Journal articles on the topic 'Regulatory ncRNAs'
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1
Lee, Yong Sun. "Are We Studying Non-Coding RNAs Correctly? Lessons from nc886." International Journal of Molecular Sciences 23, no. 8 (April 12, 2022): 4251. http://dx.doi.org/10.3390/ijms23084251.
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Non-coding RNAs (ncRNAs), such as microRNAs or long ncRNAs, have brought about a new paradigm in the regulation of gene expression. Sequencing technologies have detected transcripts with tremendous sensitivity and throughput and revealed that the majority of them lack protein-coding potential. Myriad articles have investigated numerous ncRNAs and many of them claim that ncRNAs play gene-regulatory roles. However, it is questionable whether all these articles draw conclusions through cautious gain- and loss-of function experiments whose design was reasonably based on an ncRNA’s correct identity and features. In this review, these issues are discussed with a regulatory ncRNA, nc886, as an example case to represent cautions and guidelines when studying ncRNAs.
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Chao, Haoyu, Yueming Hu, Liang Zhao, Saige Xin, Qingyang Ni, Peijing Zhang, and Ming Chen. "Biogenesis, Functions, Interactions, and Resources of Non-Coding RNAs in Plants." International Journal of Molecular Sciences 23, no. 7 (March 28, 2022): 3695. http://dx.doi.org/10.3390/ijms23073695.
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Plant transcriptomes encompass a large number of functional non-coding RNAs (ncRNAs), only some of which have protein-coding capacity. Since their initial discovery, ncRNAs have been classified into two broad categories based on their biogenesis and mechanisms of action, housekeeping ncRNAs and regulatory ncRNAs. With advances in RNA sequencing technology and computational methods, bioinformatics resources continue to emerge and update rapidly, including workflow for in silico ncRNA analysis, up-to-date platforms, databases, and tools dedicated to ncRNA identification and functional annotation. In this review, we aim to describe the biogenesis, biological functions, and interactions with DNA, RNA, protein, and microorganism of five major regulatory ncRNAs (miRNA, siRNA, tsRNA, circRNA, lncRNA) in plants. Then, we systematically summarize tools for analysis and prediction of plant ncRNAs, as well as databases. Furthermore, we discuss the silico analysis process of these ncRNAs and present a protocol for step-by-step computational analysis of ncRNAs. In general, this review will help researchers better understand the world of ncRNAs at multiple levels.
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Fu, Xiang-Dong. "Non-coding RNA: a new frontier in regulatory biology." National Science Review 1, no. 2 (May 14, 2014): 190–204. http://dx.doi.org/10.1093/nsr/nwu008.
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Abstract A striking finding in the past decade is the production of numerous non-coding RNAs (ncRNAs) from mammalian genomes. While it is entirely possible that many of those ncRNAs are transcription noises or by-products of RNA processing, increasing evidence suggests that a large fraction of them are functional and provide various regulatory activities in the cell. Thus, functional genomics and proteomics are incomplete without understanding functional ribonomics. As has been long suggested by the ‘RNA world’ hypothesis, many ncRNAs have the capacity to act like proteins in diverse biochemical processes. The enormous amount of information residing in the primary sequences and secondary structures of ncRNAs makes them particularly suited to function as scaffolds for molecular interactions. In addition, their functions appear to be stringently controlled by default via abundant nucleases when not engaged in specific interactions. This review focuses on the functional properties of regulatory ncRNAs in comparison with proteins and emphasizes both the opportunities and challenges in future ncRNA research.
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Abedi-Gaballu, Fereydoon, Elham Kamal Kazemi, Seyed Ahmad Salehzadeh, Behnaz Mansoori, Farhad Eslami, Ali Emami, Gholamreza Dehghan, Behzad Baradaran, Behzad Mansoori, and William C. Cho. "Metabolic Pathways in Breast Cancer Reprograming: An Insight to Non-Coding RNAs." Cells 11, no. 19 (September 23, 2022): 2973. http://dx.doi.org/10.3390/cells11192973.
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Cancer cells reprogram their metabolisms to achieve high energetic requirements and produce precursors that facilitate uncontrolled cell proliferation. Metabolic reprograming involves not only the dysregulation in glucose-metabolizing regulatory enzymes, but also the enzymes engaging in the lipid and amino acid metabolisms. Nevertheless, the underlying regulatory mechanisms of reprograming are not fully understood. Non-coding RNAs (ncRNAs) as functional RNA molecules cannot translate into proteins, but they do play a regulatory role in gene expression. Moreover, ncRNAs have been demonstrated to be implicated in the metabolic modulations in breast cancer (BC) by regulating the metabolic-related enzymes. Here, we will focus on the regulatory involvement of ncRNAs (microRNA, circular RNA and long ncRNA) in BC metabolism, including glucose, lipid and glutamine metabolism. Investigation of this aspect may not only alter the approaches of BC diagnosis and prognosis, but may also open a new avenue in using ncRNA-based therapeutics for BC treatment by targeting different metabolic pathways.
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Koscianska, Edyta, Emilia Kozlowska, and Agnieszka Fiszer. "Regulatory Potential of Competing Endogenous RNAs in Myotonic Dystrophies." International Journal of Molecular Sciences 22, no. 11 (June 4, 2021): 6089. http://dx.doi.org/10.3390/ijms22116089.
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Non-coding RNAs (ncRNAs) have been reported to be implicated in cell fate determination and various human diseases. All ncRNA molecules are emerging as key regulators of diverse cellular processes; however, little is known about the regulatory interaction among these various classes of RNAs. It has been proposed that the large-scale regulatory network across the whole transcriptome is mediated by competing endogenous RNA (ceRNA) activity attributed to both protein-coding and ncRNAs. ceRNAs are considered to be natural sponges of miRNAs that can influence the expression and availability of multiple miRNAs and, consequently, the global mRNA and protein levels. In this review, we summarize the current understanding of the role of ncRNAs in two neuromuscular diseases, myotonic dystrophy type 1 and 2 (DM1 and DM2), and the involvement of expanded CUG and CCUG repeat-containing transcripts in miRNA-mediated RNA crosstalk. More specifically, we discuss the possibility that long repeat tracts present in mutant transcripts can be potent miRNA sponges and may affect ceRNA crosstalk in these diseases. Moreover, we highlight practical information related to innovative disease modelling and studying RNA regulatory networks in cells. Extending knowledge of gene regulation by ncRNAs, and of complex regulatory ceRNA networks in DM1 and DM2, will help to address many questions pertinent to pathogenesis and treatment of these disorders; it may also help to better understand general rules of gene expression and to discover new rules of gene control.
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Balarezo-Cisneros, Laura Natalia, Steven Parker, Marcin G. Fraczek, Soukaina Timouma, Ping Wang, Raymond T. O’Keefe, Catherine B. Millar, and Daniela Delneri. "Functional and transcriptional profiling of non-coding RNAs in yeast reveal context-dependent phenotypes and in trans effects on the protein regulatory network." PLOS Genetics 17, no. 1 (January 25, 2021): e1008761. http://dx.doi.org/10.1371/journal.pgen.1008761.
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Non-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts. Novel functional ncRNAs, SUT125, SUT126, SUT035 and SUT532 that act in trans by modulating transcription factors were identified. Furthermore, we described the impact of SUTs and CUTs in modulating coding gene expression in response to different environmental conditions, regulating important biological process such as respiration (SUT125, SUT126, SUT035, SUT432), steroid biosynthesis (CUT494, SUT053, SUT468) or rRNA processing (SUT075 and snR30). Overall, these data capture and integrate the regulatory and phenotypic network of ncRNAs and protein-coding genes, providing genome-wide evidence of the impact of ncRNAs on cellular homeostasis.
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Fort, Rafael Sebastián, Santiago Chavez, Juan M. Trinidad Barnech, Carolina Oliveira-Rizzo, Pablo Smircich, José Roberto Sotelo-Silveira, and María Ana Duhagon. "Current Status of Regulatory Non-Coding RNAs Research in the Tritryp." Non-Coding RNA 8, no. 4 (July 18, 2022): 54. http://dx.doi.org/10.3390/ncrna8040054.
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Trypanosomatids are protozoan parasites that cause devastating vector-borne human diseases. Gene expression regulation of these organisms depends on post-transcriptional control in responding to diverse environments while going through multiple developmental stages of their complex life cycles. In this scenario, non-coding RNAs (ncRNAs) are excellent candidates for a very efficient, quick, and economic strategy to regulate gene expression. The advent of high throughput RNA sequencing technologies show the presence and deregulation of small RNA fragments derived from canonical ncRNAs. This review seeks to depict the ncRNA landscape in trypanosomatids, focusing on the small RNA fragments derived from functional RNA molecules observed in RNA sequencing studies. Small RNA fragments derived from canonical ncRNAs (tsRNAs, snsRNAs, sdRNAs, and sdrRNAs) were identified in trypanosomatids. Some of these RNAs display changes in their levels associated with different environments and developmental stages, demanding further studies to determine their functional characterization and potential roles. Nevertheless, a comprehensive and detailed ncRNA annotation for most trypanosomatid genomes is still needed, allowing better and more extensive comparative and functional studies.
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Li, Chunhua, Xiaorong Yu, Jianping Lu, Liyu Zheng, Dahua Xu, Zelong Xu, Liqiang Wang, et al. "Contributions of Gene Modules Regulated by Essential Noncoding RNA in Colon Adenocarcinoma Progression." BioMed Research International 2020 (March 24, 2020): 1–12. http://dx.doi.org/10.1155/2020/8595473.
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Noncoding RNAs (ncRNAs), especially microRNA (miRNA) and long noncoding RNA (lncRNA), have an impact on a variety of important biological processes during colon adenocarcinoma (COAD) progression. This includes chromatin organization, transcriptional and posttranscriptional regulation, and cell-cell signaling. The aim of this study is to identify the ncRNA-regulated modules that accompany the progression of COAD and to analyze their mechanisms, in order to screen the potential prognostic biomarkers for COAD. An integrative molecular analysis was carried out to identify the crosstalks of gene modules between different COAD stages, as well as the essential ncRNAs in the posttranscriptional regulation of these modules. 31 ncRNA regulatory modules were found to be significantly associated with overall survival in COAD patients. 17 out of the 31 modules (in which ncRNAs played essential roles) had improved the predictive ability for COAD patient survival compared to only the mRNAs of those modules, which were enriched in the core cancer hallmark pathways with closer interactions. These suggest that the ncRNAs’ regulatory modules not only exhibit close relation to COAD progression but also reflect the dynamic significant crosstalk of genes in the modules to the different malignant extent of COAD.
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Pandey, Amitkumar, Saiprasad Ajgaonkar, Nikita Jadhav, Praful Saha, Pranay Gurav, Sangita Panda, Dilip Mehta, and Sujit Nair. "Current Insights into miRNA and lncRNA Dysregulation in Diabetes: Signal Transduction, Clinical Trials and Biomarker Discovery." Pharmaceuticals 15, no. 10 (October 14, 2022): 1269. http://dx.doi.org/10.3390/ph15101269.
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Diabetes is one of the most frequently occurring metabolic disorders, affecting almost one tenth of the global population. Despite advances in antihyperglycemic therapeutics, the management of diabetes is limited due to its complexity and associated comorbidities, including diabetic neuropathy, diabetic nephropathy and diabetic retinopathy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are involved in the regulation of gene expression as well as various disease pathways in humans. Several ncRNAs are dysregulated in diabetes and are responsible for modulating the expression of various genes that contribute to the ‘symptom complex’ in diabetes. We review various miRNAs and lncRNAs implicated in diabetes and delineate ncRNA biological networks as well as key ncRNA targets in diabetes. Further, we discuss the spatial regulation of ncRNAs and their role(s) as prognostic markers in diabetes. We also shed light on the molecular mechanisms of signal transduction with diabetes-associated ncRNAs and ncRNA-mediated epigenetic events. Lastly, we summarize clinical trials on diabetes-associated ncRNAs and discuss the functional relevance of the dysregulated ncRNA interactome in diabetes. This knowledge will facilitate the identification of putative biomarkers for the therapeutic management of diabetes and its comorbidities. Taken together, the elucidation of the architecture of signature ncRNA regulatory networks in diabetes may enable the identification of novel biomarkers in the discovery pipeline for diabetes, which may lead to better management of this metabolic disorder.
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Gámez-Valero, Ana, Anna Guisado-Corcoll, Marina Herrero-Lorenzo, Maria Solaguren-Beascoa, and Eulàlia Martí. "Non-Coding RNAs as Sensors of Oxidative Stress in Neurodegenerative Diseases." Antioxidants 9, no. 11 (November 8, 2020): 1095. http://dx.doi.org/10.3390/antiox9111095.
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Oxidative stress (OS) results from an imbalance between the production of reactive oxygen species and the cellular antioxidant capacity. OS plays a central role in neurodegenerative diseases, where the progressive accumulation of reactive oxygen species induces mitochondrial dysfunction, protein aggregation and inflammation. Regulatory non-protein-coding RNAs (ncRNAs) are essential transcriptional and post-transcriptional gene expression controllers, showing a highly regulated expression in space (cell types), time (developmental and ageing processes) and response to specific stimuli. These dynamic changes shape signaling pathways that are critical for the developmental processes of the nervous system and brain cell homeostasis. Diverse classes of ncRNAs have been involved in the cell response to OS and have been targeted in therapeutic designs. The perturbed expression of ncRNAs has been shown in human neurodegenerative diseases, with these changes contributing to pathogenic mechanisms, including OS and associated toxicity. In the present review, we summarize existing literature linking OS, neurodegeneration and ncRNA function. We provide evidences for the central role of OS in age-related neurodegenerative conditions, recapitulating the main types of regulatory ncRNAs with roles in the normal function of the nervous system and summarizing up-to-date information on ncRNA deregulation with a direct impact on OS associated with major neurodegenerative conditions.
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McNeill, Elizabeth M., and Kendal D. Hirschi. "Roles of Regulatory RNAs in Nutritional Control." Annual Review of Nutrition 40, no. 1 (September 23, 2020): 77–104. http://dx.doi.org/10.1146/annurev-nutr-122319-035633.
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Small RNAs (sRNAs), including microRNAs (miRNAs), are noncoding RNA (ncRNA) molecules involved in gene regulation. sRNAs play important roles in development; however, their significance in nutritional control and as metabolic modulators is still emerging. The mechanisms by which diet impacts metabolic genes through miRNAs remain an important area of inquiry. Recent work has established how miRNAs are transported in body fluids often within exosomes, which are small cell-derived vesicles that function in intercellular communication. The abundance of other recently identified ncRNAs and new insights regarding ncRNAs as dietary bioactive compounds could remodel our understanding about how foods impact gene expression. Although controversial, some groups have shown that dietary RNAs from plants and animals (i.e., milk) are functional in consumers. In the future, regulating sRNAs either directly through dietary delivery or indirectly by altered expression of endogenous sRNA may be part of nutritional interventions for regulating metabolism.
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Silveira, Ana Cristina G., Kelly L. Robertson, Baochuan Lin, Zheng Wang, Gary J. Vora, Ana Tereza R. Vasconcelos, and Fabiano L. Thompson. "Identification of non-coding RNAs in environmental vibrios." Microbiology 156, no. 8 (August 1, 2010): 2452–58. http://dx.doi.org/10.1099/mic.0.039149-0.
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The discovery of non-coding RNA (ncRNA) has been mainly limited to laboratory model systems and human pathogenic bacteria. In this study, we begin to explore the ncRNA diversity in four recently sequenced environmental Vibrio species (Vibrio alginolyticus 40B, Vibrio communis 1DA3, Vibrio mimicus VM573 and Vibrio campbellii BAA-1116) by performing in silico searches using Infernal and Rfam for the identification of putative ncRNA-encoding genes. This search method resulted in the identification of 31–38 putative ncRNA genes per species and the total ncRNA catalogue spanned an assortment of regulatory mechanisms (riboswitches, cis-encoded ncRNAs, trans-encoded ncRNAs, modulators of protein activity, ribonucleoproteins, transcription termination ncRNAs and unknown). We chose to experimentally validate the identifications for V. campbellii BAA-1116 using a microarray-based expression profiling strategy. Transcript hybridization to tiled probes targeting annotated V. campbellii BAA-1116 intergenic regions revealed that 21 of the 38 predicted ncRNA genes were expressed in mid-exponential-phase cultures grown in nutrient-rich medium. The microarray findings were confirmed by testing a subset of three highly expressed (6S, tmRNA and TPP-2) and three moderately expressed (CsrB, GcvB and purine) ncRNAs via reverse transcription PCR. Our findings provide new information on the diversity of ncRNA in environmental vibrios while simultaneously promoting a more accurate annotation of genomic intergenic regions.
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Fukuda, Makiha, Toru Fujiwara, and Sho Nishida. "Roles of Non-Coding RNAs in Response to Nitrogen Availability in Plants." International Journal of Molecular Sciences 21, no. 22 (November 12, 2020): 8508. http://dx.doi.org/10.3390/ijms21228508.
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Nitrogen (N) is an essential nutrient for plant growth and development; therefore, N deficiency is a major limiting factor in crop production. Plants have evolved mechanisms to cope with N deficiency, and the role of protein-coding genes in these mechanisms has been well studied. In the last decades, regulatory non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), small interfering RNAs (siRNAs), and long ncRNAs (lncRNAs), have emerged as important regulators of gene expression in diverse biological processes. Recent advances in technologies for transcriptome analysis have enabled identification of N-responsive ncRNAs on a genome-wide scale. Characterization of these ncRNAs is expected to improve our understanding of the gene regulatory mechanisms of N response. In this review, we highlight recent progress in identification and characterization of N-responsive ncRNAs in Arabidopsis thaliana and several other plant species including maize, rice, and Populus.
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TSENG, HUEI-HUN, ZASHA WEINBERG, JEREMY GORE, RONALD R. BREAKER, and WALTER L. RUZZO. "FINDING NON-CODING RNAs THROUGH GENOME-SCALE CLUSTERING." Journal of Bioinformatics and Computational Biology 07, no. 02 (April 2009): 373–88. http://dx.doi.org/10.1142/s0219720009004126.
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Non-coding RNAs (ncRNAs) are transcripts that do not code for proteins. Recent findings have shown that RNA-mediated regulatory mechanisms influence a substantial portion of typical microbial genomes. We present an efficient method for finding potential ncRNAs in bacteria by clustering genomic sequences based on homology inferred from both primary sequence and secondary structure. We evaluate our approach using a set of predominantly Firmicutes sequences. Our results showed that, though primary sequence based–homology search was inaccurate for diverged ncRNA sequences, through our clustering method, we were able to infer motifs that recovered nearly all members of most known ncRNA families. Hence, our method shows promise for discovering new families of ncRNA.
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Žarković, Milena, Franziska Hufsky, Udo R. Markert, and Manja Marz. "The Role of Non-Coding RNAs in the Human Placenta." Cells 11, no. 9 (May 9, 2022): 1588. http://dx.doi.org/10.3390/cells11091588.
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Non-coding RNAs (ncRNAs) play a central and regulatory role in almost all cells, organs, and species, which has been broadly recognized since the human ENCODE project and several other genome projects. Nevertheless, a small fraction of ncRNAs have been identified, and in the placenta they have been investigated very marginally. To date, most examples of ncRNAs which have been identified to be specific for fetal tissues, including placenta, are members of the group of microRNAs (miRNAs). Due to their quantity, it can be expected that the fairly larger group of other ncRNAs exerts far stronger effects than miRNAs. The syncytiotrophoblast of fetal origin forms the interface between fetus and mother, and releases permanently extracellular vesicles (EVs) into the maternal circulation which contain fetal proteins and RNA, including ncRNA, for communication with neighboring and distant maternal cells. Disorders of ncRNA in placental tissue, especially in trophoblast cells, and in EVs seem to be involved in pregnancy disorders, potentially as a cause or consequence. This review summarizes the current knowledge on placental ncRNA, their transport in EVs, and their involvement and pregnancy pathologies, as well as their potential for novel diagnostic tools.
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Mukherjee, Anirban Goutam, Uddesh Ramesh Wanjari, Abilash Valsala Gopalakrishnan, Ramkumar Katturajan, Sandra Kannampuzha, Reshma Murali, Arunraj Namachivayam, et al. "Exploring the Regulatory Role of ncRNA in NAFLD: A Particular Focus on PPARs." Cells 11, no. 24 (December 7, 2022): 3959. http://dx.doi.org/10.3390/cells11243959.
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Liver diseases are responsible for global mortality and morbidity and are a significant cause of death worldwide. Consequently, the advancement of new liver disease targets is of great interest. Non-coding RNA (ncRNA), such as microRNA (miRNA) and long ncRNA (lncRNA), has been proven to play a significant role in the pathogenesis of virtually all acute and chronic liver disorders. Recent studies demonstrated the medical applications of miRNA in various phases of hepatic pathology. PPARs play a major role in regulating many signaling pathways involved in various metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, encompassing a spectrum spanning from mild steatosis to severe non-alcoholic steatohepatitis (NASH). PPARs were found to be one of the major regulators in the progression of NAFLD. There is no recognized treatment for NAFLD, even though numerous clinical trials are now underway. NAFLD is a major risk factor for developing hepatocellular carcinoma (HCC), and its frequency increases as obesity and diabetes become more prevalent. Reprogramming anti-diabetic and anti-obesity drugs is an effective therapy option for NAFLD and NASH. Several studies have also focused on the role of ncRNAs in the pathophysiology of NAFLD. The regulatory effects of these ncRNAs make them a primary target for treatments and as early biomarkers. In this study, the main focus will be to understand the regulation of PPARs through ncRNAs and their role in NAFLD.
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Bhogireddy, Sailaja, Satendra K. Mangrauthia, Rakesh Kumar, Arun K. Pandey, Sadhana Singh, Ankit Jain, Hikmet Budak, Rajeev K. Varshney, and Himabindu Kudapa. "Regulatory non-coding RNAs: a new frontier in regulation of plant biology." Functional & Integrative Genomics 21, no. 3-4 (May 20, 2021): 313–30. http://dx.doi.org/10.1007/s10142-021-00787-8.
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AbstractBeyond the most crucial roles of RNA molecules as a messenger, ribosomal, and transfer RNAs, the regulatory role of many non-coding RNAs (ncRNAs) in plant biology has been recognized. ncRNAs act as riboregulators by recognizing specific nucleic acid targets through homologous sequence interactions to regulate plant growth, development, and stress responses. Regulatory ncRNAs, ranging from small to long ncRNAs (lncRNAs), exert their control over a vast array of biological processes. Based on the mode of biogenesis and their function, ncRNAs evolved into different forms that include microRNAs (miRNAs), small interfering RNAs (siRNAs), miRNA variants (isomiRs), lncRNAs, circular RNAs (circRNAs), and derived ncRNAs. This article explains the different classes of ncRNAs and their role in plant development and stress responses. Furthermore, the applications of regulatory ncRNAs in crop improvement, targeting agriculturally important traits, have been discussed.
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Ofoeyeno, Nduka, Emmanuel Ekpenyong, and Chiara Braconi. "Pathogenetic Role and Clinical Implications of Regulatory RNAs in Biliary Tract Cancer." Cancers 13, no. 1 (December 22, 2020): 12. http://dx.doi.org/10.3390/cancers13010012.
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Biliary tract cancer (BTC) is characterised by poor prognosis and low overall survival in patients. This is generally due to minimal understanding of its pathogenesis, late diagnosis and limited therapeutics in preventing or treating BTC patients. Non-coding RNA (ncRNA) are small RNAs (mRNA) that are not translated to proteins. ncRNAs were considered to be of no importance in the genome, but recent studies have shown they play essential roles in biology and oncology such as transcriptional repression and degradation, thus regulating mRNA transcriptomes. This has led to investigations into the role of ncRNAs in the pathogenesis of BTC, and their clinical implications. In this review, the mechanisms of action of ncRNA are discussed and the role of microRNAs in BTC is summarised. The scope of this review will be limited to miRNA as they have been shown to play the most significant roles in BTC progression. There is huge potential in miRNA-based biomarkers and therapeutics in BTC, but more studies, research and technological advancements are required before it can be translated into clinical practice for patients.
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Tschumper, Renee C., Dominique B. Hoelzinger, Denise K. Walters, Jaime I. Davila, Collin A. Osborne, and Diane F. Jelinek. "Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells." Non-Coding RNA 8, no. 1 (February 5, 2022): 15. http://dx.doi.org/10.3390/ncrna8010015.
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The differentiation of B cells into antibody secreting plasma cells (PCs) is governed by a strict regulatory network that results in expression of specific transcriptomes along the activation continuum. In vitro models yielding significant numbers of PCs phenotypically identical to the in vivo state enable investigation of pathways, metabolomes, and non-coding (ncRNAs) not previously identified. The objective of our study was to characterize ncRNA expression during human B cell activation and differentiation. To achieve this, we used an in vitro system and performed RNA-seq on resting and activated B cells and PCs. Characterization of coding gene transcripts, including immunoglobulin (Ig), validated our system and also demonstrated that memory B cells preferentially differentiated into PCs. Importantly, we identified more than 980 ncRNA transcripts that are differentially expressed across the stages of activation and differentiation, some of which are known to target transcription, proliferation, cytoskeletal, autophagy and proteasome pathways. Interestingly, ncRNAs located within Ig loci may be targeting both Ig and non-Ig-related transcripts. ncRNAs associated with B cell malignancies were also identified. Taken together, this system provides a platform to study the role of specific ncRNAs in B cell differentiation and altered expression of those ncRNAs involved in B cell malignancies.
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Soleimani, Saeed, Zahra Valizadeh Arshad, Sharif Moradi, Ali Ahmadi, Seyed Javad Davarpanah, and Sadegh Azimzadeh Jamalkandi. "Small regulatory noncoding RNAs in Drosophila melanogaster: biogenesis and biological functions." Briefings in Functional Genomics 19, no. 4 (March 27, 2020): 309–23. http://dx.doi.org/10.1093/bfgp/elaa005.
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Abstract RNA interference (RNAi) is an important phenomenon that has diverse genetic regulatory functions at the pre- and posttranscriptional levels. The major trigger for the RNAi pathway is double-stranded RNA (dsRNA). dsRNA is processed to generate various types of major small noncoding RNAs (ncRNAs) that include microRNAs (miRNAs), small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs) in Drosophila melanogaster (D. melanogaster). Functionally, these small ncRNAs play critical roles in virtually all biological systems and developmental pathways. Identification and processing of dsRNAs and activation of RNAi machinery are the three major academic interests that surround RNAi research. Mechanistically, some of the important biological functions of RNAi are achieved through: (i) supporting genomic stability via degradation of foreign viral genomes; (ii) suppressing the movement of transposable elements and, most importantly, (iii) post-transcriptional regulation of gene expression by miRNAs that contribute to regulation of epigenetic modifications such as heterochromatin formation and genome imprinting. Here, we review various routes of small ncRNA biogenesis, as well as different RNAi-mediated pathways in D. melanogaster with a particular focus on signaling pathways. In addition, a critical discussion of the most relevant and latest findings that concern the significant contribution of small ncRNAs to the regulation of D. melanogaster physiology and pathophysiology is presented.
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Patty, Benjamin J., and Sarah J. Hainer. "Non-Coding RNAs and Nucleosome Remodeling Complexes: An Intricate Regulatory Relationship." Biology 9, no. 8 (August 7, 2020): 213. http://dx.doi.org/10.3390/biology9080213.
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Eukaryotic genomes are pervasively transcribed, producing both coding and non-coding RNAs (ncRNAs). ncRNAs are diverse and a critical family of biological molecules, yet much remains unknown regarding their functions and mechanisms of regulation. ATP-dependent nucleosome remodeling complexes, in modifying chromatin structure, play an important role in transcriptional regulation. Recent findings show that ncRNAs regulate nucleosome remodeler activities at many levels and that ncRNAs are regulatory targets of nucleosome remodelers. Further, a series of recent screens indicate this network of regulatory interactions is more expansive than previously appreciated. Here, we discuss currently described regulatory interactions between ncRNAs and nucleosome remodelers and contextualize their biological functions.
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Cerchia, Laura, and Vittorio De Franciscis. "Noncoding RNAs in Cancer Medicine." Journal of Biomedicine and Biotechnology 2006 (2006): 1–8. http://dx.doi.org/10.1155/jbb/2006/73104.
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Several signalling proteins involved in cell growth and differentiation represent attractive candidate targets for cancer diagnosis and/or therapy since they can act as oncogenes. Because of their high specificity and low immunogeneicity, using artificial small noncoding RNA (ncRNAs) as therapeutics has recently become a highly promising and rapidly expanding field of interest. Indeed, ncRNAs may either interfere with RNA transcription, stability, translation or directly hamper the function of the targets by binding to their surface. The recent finding that the expression of several genes is under the control of small single-stranded regulatory RNAs, including miRNAs, makes these genes as appropriate targets for ncRNA gene silencing. Furthermore, another class of small ncRNA, aptamers, act as high-affinity ligands and potential antagonists of disease-associated proteins. We will review here the recent and innovative methods that have been developed and the possible applications of ncRNAs as inhibitors or tracers in cancer medicine.
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Chen, Chong, Haining Tan, Jiaqi Bi, Zheng Li, Tianhua Rong, Youxi Lin, Liang Sun, Xingye Li, and Jianxiong Shen. "Identification of Competing Endogenous RNA Regulatory Networks in Vitamin A Deficiency-Induced Congenital Scoliosis by Transcriptome Sequencing Analysis." Cellular Physiology and Biochemistry 48, no. 5 (2018): 2134–46. http://dx.doi.org/10.1159/000492556.
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Background/Aims: Congenital scoliosis (CS) is a result of anomalous development of vertebrae and is frequently associated with somitogenesis malformation. Although noncoding RNAs (ncRNAs) have been recently determined to be involved in the pathogenesis of CS, the competing endogenous RNA (ceRNA) regulatory networks in CS remain largely unknown. Methods: Sequencing was conducted to explore the ncRNA expression profiles in rat embryos (gestation day 9) following vitamin A deficiency (VAD) (n = 9 for the vitamin A deficiency-induced congenital scoliosis (VAD-CS) group and n = 4 for the control group). Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was conducted to verify the expression levels of selected mRNAs, long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). Bioinformatics analysis was used to discover the possible relationships and functions of the ceRNAs. Results: A total of 749 mRNAs, 56 miRNAs, 685 lncRNAs, and 70 circRNAs were identified to have significantly different expression levels in the two groups. Wnt, PI3K-ATK, FoxO, EGFR, and mTOR were found to be the most significant pathways involved in VAD-CS pathogenesis. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of CS were built, and the gene expression mechanisms regulated by ncRNAs were unveiled via the ceRNA regulatory networks. Conclusion: We comprehensively identified ceRNA regulatory networks of embryonic somite development in VAD-CS as well as revealed the contribution of different ncRNA expression profiles. Our data demonstrate the association between mRNAs and ncRNAs in the pathogenic mechanism of CS.
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Chen, Yifan, Paul S. Thomas, Rakesh K. Kumar, and Cristan Herbert. "The role of noncoding RNAs in regulating epithelial responses in COPD." American Journal of Physiology-Lung Cellular and Molecular Physiology 315, no. 2 (August 1, 2018): L184—L192. http://dx.doi.org/10.1152/ajplung.00063.2018.
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Chronic obstructive pulmonary disease (COPD), one of the leading causes of death in the world, is a chronic inflammatory disease of the airways usually caused by long-term exposure to inhaled irritants. Airway epithelial cells (AECs) play a key role in initializing COPD and driving the exacerbation of this disease through the release of various cytokines. This AEC-derived cytokine response is tightly regulated possibly through the regulatory effects of noncoding RNAs (ncRNAs). Although the importance of ncRNAs in pulmonary diseases has been increasingly realized, little is known about the role of ncRNA in the regulation of inflammatory responses in COPD. This review outlines the features of AEC-derived cytokine responses in COPD and how ncRNAs regulate these inflammatory responses.
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Cai, Li, Jiajia Xuan, Qiao Lin, Junhao Wang, Shurong Liu, Fangzhou Xie, Lingling Zheng, Bin Li, Lianghu Qu, and Jianhua Yang. "Pol3Base: a resource for decoding the interactome, expression, evolution, epitranscriptome and disease variations of Pol III-transcribed ncRNAs." Nucleic Acids Research 50, no. D1 (November 8, 2021): D279—D286. http://dx.doi.org/10.1093/nar/gkab1033.
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Abstract RNA polymerase III (Pol III) transcribes hundreds of non-coding RNA genes (ncRNAs), which involve in a variety of cellular processes. However, the expression, functions, regulatory networks and evolution of these Pol III-transcribed ncRNAs are still largely unknown. In this study, we developed a novel resource, Pol3Base (http://rna.sysu.edu.cn/pol3base/), to decode the interactome, expression, evolution, epitranscriptome and disease variations of Pol III-transcribed ncRNAs. The current release of Pol3Base includes thousands of regulatory relationships between ∼79 000 ncRNAs and transcription factors by mining 56 ChIP-seq datasets. By integrating CLIP-seq datasets, we deciphered the interactions of these ncRNAs with >240 RNA binding proteins. Moreover, Pol3Base contains ∼9700 RNA modifications located within thousands of Pol III-transcribed ncRNAs. Importantly, we characterized expression profiles of ncRNAs in >70 tissues and 28 different tumor types. In addition, by comparing these ncRNAs from human and mouse, we revealed about 4000 evolutionary conserved ncRNAs. We also identified ∼11 403 tRNA-derived small RNAs (tsRNAs) in 32 different tumor types. Finally, by analyzing somatic mutation data, we investigated the mutation map of these ncRNAs to help uncover their potential roles in diverse diseases. This resource will help expand our understanding of potential functions and regulatory networks of Pol III-transcribed ncRNAs.
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Grimaldi, Alessio, Giuseppe Pietropaolo, Helena Stabile, Andrea Kosta, Cristina Capuano, Angela Gismondi, Angela Santoni, Giuseppe Sciumè, and Cinzia Fionda. "The Regulatory Activity of Noncoding RNAs in ILCs." Cells 10, no. 10 (October 14, 2021): 2742. http://dx.doi.org/10.3390/cells10102742.
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Innate lymphoid cells (ILCs) are innate lymphocytes playing essential functions in protection against microbial infections and participate in both homeostatic and pathological contexts, including tissue remodeling, cancer, and inflammatory disorders. A number of lineage-defining transcription factors concurs to establish transcriptional networks which determine the identity and the activity of the distinct ILC subsets. However, the contribution of other regulatory molecules in controlling ILC development and function is also recently emerging. In this regard, noncoding RNAs (ncRNAs) represent key elements of the complex regulatory network of ILC biology and host protection. ncRNAs mostly lack protein-coding potential, but they are endowed with a relevant regulatory activity in immune and nonimmune cells because of their ability to control chromatin structure, RNA stability, and/or protein synthesis. Herein, we summarize recent studies describing how distinct types of ncRNAs, mainly microRNAs, long ncRNAs, and circular RNAs, act in the context of ILC biology. In particular, we comment on how ncRNAs can exert key effects in ILCs by controlling gene expression in a cell- or state-specific manner and how this tunes distinct functional outputs in ILCs.
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Iesato, Asumi, and Carmelo Nucera. "Role of Regulatory Non-Coding RNAs in Aggressive Thyroid Cancer: Prospective Applications of Neural Network Analysis." Molecules 26, no. 10 (May 19, 2021): 3022. http://dx.doi.org/10.3390/molecules26103022.
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Thyroid cancer (TC) is the most common endocrine malignancy. Most TCs have a favorable prognosis, whereas anaplastic thyroid carcinoma (ATC) is a lethal form of cancer. Different genetic and epigenetic alterations have been identified in aggressive forms of TC such as ATC. Non-coding RNAs (ncRNAs) represent functional regulatory molecules that control chromatin reprogramming, including transcriptional and post-transcriptional mechanisms. Intriguingly, they also play an important role as coordinators of complex gene regulatory networks (GRNs) in cancer. GRN analysis can model molecular regulation in different species. Neural networks are robust computing systems for learning and modeling the dynamics or dependencies between genes, and are used for the reconstruction of large data sets. Canonical network motifs are coordinated by ncRNAs through gene production from each transcript as well as through the generation of a single transcript that gives rise to multiple functional products by post-transcriptional modifications. In non-canonical network motifs, ncRNAs interact through binding to proteins and/or protein complexes and regulate their functions. This article overviews the potential role of ncRNAs GRNs in TC. It also suggests prospective applications of deep neural network analysis to predict ncRNA molecular language for early detection and to determine the prognosis of TC. Validation of these analyses may help in the design of more effective and precise targeted therapies against aggressive TC.
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Yazgan, Oya, and Jocelyn E. Krebs. "Noncoding but nonexpendable: transcriptional regulation by large noncoding RNA in eukaryotesThis paper is one of a selection of papers published in this Special Issue, entitled 28th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process." Biochemistry and Cell Biology 85, no. 4 (August 2007): 484–96. http://dx.doi.org/10.1139/o07-061.
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Genome sequencing and annotation has advanced our understanding of genome organization and gene structure but initially only allowed predictions of how many genes might be present. Mechanisms such as alternative splicing reveal that these predictions only scratch the surface of the true nature of the transcriptome. Several thousand expressed partial gene fragments have been cloned but were considered transcriptional noise or cloning artifacts. We now know that genomes are indeed expressed at much higher levels than was previously predicted, and much of the additional transcription maps to intergenic regions, intron sequences, and untranslated regions of mRNAs. These transcripts are expressed from either the sense or the antisense strand and can be confirmed by conventional techniques. In addition to the already established roles for small RNAs in gene regulation, large noncoding RNAs (ncRNAs) are also emerging as potent regulators of gene expression. In this review, we summarize several illustrative examples of gene regulatory mechanisms that involve large ncRNAs. We describe several distinct regulatory mechanisms that involve large ncRNAs, such as transcriptional interference and promoter inactivation, as well as indirect effects on transcription regulatory proteins and in genomic imprinting. These diverse functions for large ncRNAs are likely to be only the first of many novel regulatory mechanisms emerging from this growing field.
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Lu, Jianan, Yujie Luo, Shuhao Mei, Yuanjian Fang, Jianmin Zhang, and Sheng Chen. "The Effect of Melatonin Modulation of Non-coding RNAs on Central Nervous System Disorders: An Updated Review." Current Neuropharmacology 19, no. 1 (December 31, 2020): 3–23. http://dx.doi.org/10.2174/1570159x18666200503024700.
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: Melatonin is a hormone produced in and secreted by the pineal gland. Besides its role in regulating circadian rhythms, melatonin has a wide range of protective functions in the central nervous system (CNS) disorders. The mechanisms underlying this protective function are associated with the regulatory effects of melatonin on related genes and proteins. In addition to messenger ribonucleic acid (RNA) that can be translated into protein, an increasing number of non-coding RNAs in the human body are proven to participate in many diseases. This review discusses the current progress of research on the effects of melatonin modulation of non-coding RNAs (ncRNAs), including microRNA, long ncRNA, and circular RNA. The role of melatonin in regulating common pathological mechanisms through these ncRNAs is also summarized. Furthermore, the ncRNAs, currently shown to be involved in melatonin signaling in CNS diseases, are discussed. The information compiled in this review will open new avenues for future research into melatonin mechanisms and provide a further understanding of ncRNAs in the CNS.
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Figueiredo, Joana, Tiago Santos, André Miranda, Daniela Alexandre, Bernardo Teixeira, Pedro Simões, Jéssica Lopes-Nunes, and Carla Cruz. "Ligands as Stabilizers of G-Quadruplexes in Non-Coding RNAs." Molecules 26, no. 20 (October 13, 2021): 6164. http://dx.doi.org/10.3390/molecules26206164.
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The non-coding RNAs (ncRNA) are RNA transcripts with different sizes, structures and biological functions that do not encode functional proteins. RNA G-quadruplexes (rG4s) have been found in small and long ncRNAs. The existence of an equilibrium between rG4 and stem−loop structures in ncRNAs and its effect on biological processes remains unexplored. For example, deviation from the stem−loop leads to deregulated mature miRNA levels, demonstrating that miRNA biogenesis can be modulated by ions or small molecules. In light of this, we report several examples of rG4s in certain types of ncRNAs, and the implications of G4 stabilization using small molecules, also known as G4 ligands, in the regulation of gene expression, miRNA biogenesis, and miRNA−mRNA interactions. Until now, different G4 ligands scaffolds were synthesized for these targets. The regulatory role of the above-mentioned rG4s in ncRNAs can be used as novel therapeutic approaches for adjusting miRNA levels.
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Torsin, Ligia I., George E. D. Petrescu, Alexandru A. Sabo, Baoqing Chen, Felix M. Brehar, Mihnea P. Dragomir, and George A. Calin. "Editing and Chemical Modifications on Non-Coding RNAs in Cancer: A New Tale with Clinical Significance." International Journal of Molecular Sciences 22, no. 2 (January 8, 2021): 581. http://dx.doi.org/10.3390/ijms22020581.
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Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: m5C, hm5C, m6A, m1A, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered “non-functional” ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer it is possible to translate the knowledge about ncRNAs and their modifications into clinical practice.
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Torsin, Ligia I., George E. D. Petrescu, Alexandru A. Sabo, Baoqing Chen, Felix M. Brehar, Mihnea P. Dragomir, and George A. Calin. "Editing and Chemical Modifications on Non-Coding RNAs in Cancer: A New Tale with Clinical Significance." International Journal of Molecular Sciences 22, no. 2 (January 8, 2021): 581. http://dx.doi.org/10.3390/ijms22020581.
Full textAbstract:
Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: m5C, hm5C, m6A, m1A, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered “non-functional” ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer it is possible to translate the knowledge about ncRNAs and their modifications into clinical practice.
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Zhang, Yuwei, Dechao Bu, Peipei Huo, Zhihao Wang, Hao Rong, Yanguo Li, Jingjia Liu, et al. "ncFANs v2.0: an integrative platform for functional annotation of non-coding RNAs." Nucleic Acids Research 49, W1 (May 29, 2021): W459—W468. http://dx.doi.org/10.1093/nar/gkab435.
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Abstract Increasing evidence proves the essential regulatory roles of non-coding RNAs (ncRNAs) in biological processes. However, characterizing the specific functions of ncRNAs remains a challenging task, owing to the intensive consumption of the experimental approaches. Here, we present an online platform ncFANs v2.0 that is a significantly enhanced version of our previous ncFANs to provide multiple computational methods for ncRNA functional annotation. Specifically, ncFANs v2.0 was updated to embed three functional modules, including ncFANs-NET, ncFANs-eLnc and ncFANs-CHIP. ncFANs-NET is a new module designed for data-free functional annotation based on four kinds of pre-built networks, including the co-expression network, co-methylation network, long non-coding RNA (lncRNA)-centric regulatory network and random forest-based network. ncFANs-eLnc enables the one-stop identification of enhancer-derived lncRNAs from the de novo assembled transcriptome based on the user-defined or our pre-annotated enhancers. Moreover, ncFANs-CHIP inherits the original functions for microarray data-based functional annotation and supports more chip types. We believe that our ncFANs v2.0 carries sufficient convenience and practicability for biological researchers and facilitates unraveling the regulatory mechanisms of ncRNAs. The ncFANs v2.0 server is freely available at http://bioinfo.org/ncfans or http://ncfans.gene.ac.
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Glasgow, Arlene M. A., Chiara De Santi, and Catherine M. Greene. "Non-coding RNA in cystic fibrosis." Biochemical Society Transactions 46, no. 3 (May 9, 2018): 619–30. http://dx.doi.org/10.1042/bst20170469.
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Non-coding RNAs (ncRNAs) are an abundant class of RNAs that include small ncRNAs, long non-coding RNAs (lncRNA) and pseudogenes. The human ncRNA atlas includes thousands of these specialised RNA molecules that are further subcategorised based on their size or function. Two of the more well-known and widely studied ncRNA species are microRNAs (miRNAs) and lncRNAs. These are regulatory RNAs and their altered expression has been implicated in the pathogenesis of a variety of human diseases. Failure to express a functional cystic fibrosis (CF) transmembrane receptor (CFTR) chloride ion channel in epithelial cells underpins CF. Secondary to the CFTR defect, it is known that other pathways can be altered and these may contribute to the pathophysiology of CF lung disease in particular. For example, quantitative alterations in expression of some ncRNAs are associated with CF. In recent years, there has been a series of published studies exploring ncRNA expression and function in CF. The majority have focussed principally on miRNAs, with just a handful of reports to date on lncRNAs. The present study reviews what is currently known about ncRNA expression and function in CF, and discusses the possibility of applying this knowledge to the clinical management of CF in the near future.
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Xiao, Dandan, Min Chen, Xiaoqian Yang, Hai Bao, Yuzhang Yang, and Yanwei Wang. "The Intersection of Non-Coding RNAs Contributes to Forest Trees’ Response to Abiotic Stress." International Journal of Molecular Sciences 23, no. 12 (June 7, 2022): 6365. http://dx.doi.org/10.3390/ijms23126365.
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Non-coding RNAs (ncRNAs) play essential roles in plants by modulating the expression of genes at the transcriptional or post-transcriptional level. In recent years, ncRNAs have been recognized as crucial regulators for growth and development in forest trees, and ncRNAs that respond to various abiotic stresses are now under intense study. In this review, we summarized recent advances in the understanding of abiotic stress-responsive microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in forest trees. Furthermore, we analyzed the intersection of miRNAs, and epigenetic modified ncRNAs of forest trees in response to abiotic stress. In particular, the abiotic stress-related lncRNA/circRNA–miRNA–mRNA regulatory network of forest trees was explored.
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Nie, Li, Zhang, and Liu. "Roles of Non-Coding RNAs in Normal Human Brain Development, Brain Tumor, and Neuropsychiatric Disorders." Non-Coding RNA 5, no. 2 (April 30, 2019): 36. http://dx.doi.org/10.3390/ncrna5020036.
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One of modern biology’s great surprises is that the human genome encodes only ~20,000 protein-coding genes, which represents less than 2% of the total genome sequence, and the majority of them are transcribed into non-coding RNAs (ncRNAs). Increasing evidence has shown that ncRNAs, including miRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play important roles in regulating a wide range of biological processes of the human brain. They not only regulate the pathogenesis of brain tumors, but also the development of neuropsychiatric diseases. This review provides an integrated overview of the roles of ncRNAs in normal human brain function, brain tumor development, and neuropsychiatric disease. We discussed the functions and molecular mechanisms of miRNAs, lncRNAs, and circRNAs in normal brain function and glioma, respectively, including those in exosome vesicles that can act as a molecular information carrier. We also discussed the regulatory roles of ncRNAs in the development of neuropsychiatric diseases. Lastly, we summarized the currently available platforms and tools that can be used for ncRNA identification and functional exploration in human diseases. This study will provide comprehensive insights for the roles of ncRNAs in human brain function and disease.
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Xu, Ya-Jie, Pei-Pei Liu, Shyh-Chang Ng, Zhao-Qian Teng, and Chang-Mei Liu. "Regulatory networks between Polycomb complexes and non-coding RNAs in the central nervous system." Journal of Molecular Cell Biology 12, no. 5 (July 10, 2019): 327–36. http://dx.doi.org/10.1093/jmcb/mjz058.
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Abstract High-throughput sequencing has facilitated the identification of many types of non-coding RNAs (ncRNAs) involved in diverse cellular processes. NcRNAs as epigenetic mediators play key roles in neuronal development, maintenance, and dysfunction by controlling gene expression at multiple levels. NcRNAs may not only target specific DNA or RNA for gene silence but may also directly interact with chromatin-modifying proteins like Polycomb group (PcG) proteins to drive orchestrated transcriptional programs. Recent significant progress has been made in characterizing ncRNAs and PcG proteins involved in transcriptional, post-transcriptional, and epigenetic regulation. More importantly, dysregulation of ncRNAs, PcG proteins, and interplay among them is closely associated with the pathogenesis of central nervous system (CNS) disorders. In this review, we focus on the interplay between ncRNAs and PcG proteins in the CNS and highlight the functional roles of the partnership during neural development and diseases.
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Min, Jie, Wenjun Liu, and Jing Li. "Emerging Role of Interferon-Induced Noncoding RNA in Innate Antiviral Immunity." Viruses 14, no. 12 (November 23, 2022): 2607. http://dx.doi.org/10.3390/v14122607.
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Thousands of unique noncoding RNAs (ncRNAs) exist within the genomes of higher eukaryotes. Upon virus infection, the host generates interferons (IFNs), which initiate the expression of hundreds of interferon-stimulated genes (ISGs) through IFN receptors on the cell surface, establishing a barrier as the host’s antiviral innate immunity. With the development of novel RNA-sequencing technology, many IFN-induced ncRNAs have been identified, and increasing attention has been given to their functions as regulators involved in the antiviral innate immune response. IFN-induced ncRNAs regulate the expression of viral proteins, IFNs, and ISGs, as well as host genes that are critical for viral replication, cytokine and chemokine production, and signaling pathway activation. This review summarizes the complex regulatory role of IFN-induced ncRNAs in antiviral innate immunity from the above aspects, aiming to improve understanding of ncRNAs and provide reference for the basic research of antiviral innate immunity.
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Ma, Xu, Fei Zhao, and Bo Zhou. "The Characters of Non-Coding RNAs and Their Biological Roles in Plant Development and Abiotic Stress Response." International Journal of Molecular Sciences 23, no. 8 (April 8, 2022): 4124. http://dx.doi.org/10.3390/ijms23084124.
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Plant growth and development are greatly affected by the environment. Many genes have been identified to be involved in regulating plant development and adaption of abiotic stress. Apart from protein-coding genes, more and more evidence indicates that non-coding RNAs (ncRNAs), including small RNAs and long ncRNAs (lncRNAs), can target plant developmental and stress-responsive mRNAs, regulatory genes, DNA regulatory regions, and proteins to regulate the transcription of various genes at the transcriptional, posttranscriptional, and epigenetic level. Currently, the molecular regulatory mechanisms of sRNAs and lncRNAs controlling plant development and abiotic response are being deeply explored. In this review, we summarize the recent research progress of small RNAs and lncRNAs in plants, focusing on the signal factors, expression characters, targets functions, and interplay network of ncRNAs and their targets in plant development and abiotic stress responses. The complex molecular regulatory pathways among small RNAs, lncRNAs, and targets in plants are also discussed. Understanding molecular mechanisms and functional implications of ncRNAs in various abiotic stress responses and development will benefit us in regard to the use of ncRNAs as potential character-determining factors in molecular plant breeding.
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Donati, Simone, Cinzia Aurilia, Gaia Palmini, Irene Falsetti, Teresa Iantomasi, and Maria Luisa Brandi. "Autophagy-Related ncRNAs in Pancreatic Cancer." Pharmaceuticals 15, no. 12 (December 13, 2022): 1547. http://dx.doi.org/10.3390/ph15121547.
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Pancreatic cancer (PC) is a malignancy accounting for only 3% of total cancers, but with a low 5-year relative survival rate. Approximately 80% of PC patients are diagnosed at a late stage when the disease has already spread from the primary site. Despite advances in PC treatment, there is an urgently needed for the identification of novel therapeutic strategies for PC, particularly for patients who cannot undergo classical surgery. Autophagy is an evolutionarily conserved process used by cells to adapt to metabolic stress via the degrading or recycling of damaged or unnecessary organelles and cellular components. This process is elevated in PC and, thus, it contributes to the onset, progression, and cancer cell resistance to chemotherapy in pancreatic tumors. Autophagy inhibition has been shown to lead to cancer regression and to increase the sensitivity of pancreatic cells to radiation and chemotherapy. Emerging studies have focused on the roles of non-coding RNAs (ncRNAs), such as miRNAs, long non-coding RNAs, and circular RNAs, in PC development and progression. Furthermore, ncRNAs have been reported as crucial regulators of many biological processes, including autophagy, suggesting that ncRNA-based autophagy targeting methods could be promising novel molecular approaches for specifically reducing autophagic flux, thus improving the management of PC patients. In this review, we briefly summarize the existing studies regarding the role and the regulatory mechanisms of autophagy-related ncRNAs in the context of this cancer.
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DeOcesano-Pereira, Carlos, Raquel A. C. Machado, Ana Marisa Chudzinski-Tavassi, and Mari Cleide Sogayar. "Emerging Roles and Potential Applications of Non-Coding RNAs in Glioblastoma." International Journal of Molecular Sciences 21, no. 7 (April 9, 2020): 2611. http://dx.doi.org/10.3390/ijms21072611.
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Non-coding RNAs (ncRNAs) comprise a diversity of RNA species, which do not have the potential to encode proteins. Non-coding RNAs include two classes of RNAs, namely: short regulatory ncRNAs and long non-coding RNAs (lncRNAs). The short regulatory RNAs, containing up to 200 nucleotides, include small RNAs, such as microRNAs (miRNA), short interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs). The lncRNAs include long antisense RNAs and long intergenic RNAs (lincRNAs). Non-coding RNAs have been implicated as master regulators of several biological processes, their expression being strictly regulated under physiological conditions. In recent years, particularly in the last decade, substantial effort has been made to investigate the function of ncRNAs in several human diseases, including cancer. Glioblastoma is the most common and aggressive type of brain cancer in adults, with deregulated expression of small and long ncRNAs having been implicated in onset, progression, invasiveness, and recurrence of this tumor. The aim of this review is to guide the reader through important aspects of miRNA and lncRNA biology, focusing on the molecular mechanism associated with the progression of this highly malignant cancer type.
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Riaz, Farooq, and Dongmin Li. "Non-coding RNA Associated Competitive Endogenous RNA Regulatory Network: Novel Therapeutic Approach in Liver Fibrosis." Current Gene Therapy 19, no. 5 (December 27, 2019): 305–17. http://dx.doi.org/10.2174/1566523219666191107113046.
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Liver fibrosis or scarring is the most common pathological feature caused by chronic liver injury, and is widely considered one of the primary causes of morbidity and mortality. It is primarily characterised by hepatic stellate cells (HSC) activation and excessive extracellular matrix (ECM) protein deposition. Overwhelming evidence suggests that the dysregulation of several noncoding RNAs (ncRNAs), mainly long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) contributes to the activation of HSC and progression of liver fibrosis. These ncRNAs not only bind to their target genes for the development and regression of liver fibrosis but also act as competing endogenous RNAs (ceRNAs) by sponging with miRNAs to form signaling cascades. Among these signaling cascades, lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA are critical modulators for the initiation, progression, and regression of liver fibrosis. Thus, targeting these interacting ncRNA cascades can serve as a novel and potential therapeutic target for inhibition of HSC activation and prevention and regression of liver fibrosis.
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Cheong, Jit Kong, Dimple Rajgor, Yang Lv, Ka Yan Chung, Yew Chung Tang, and He Cheng. "Noncoding RNome as Enabling Biomarkers for Precision Health." International Journal of Molecular Sciences 23, no. 18 (September 8, 2022): 10390. http://dx.doi.org/10.3390/ijms231810390.
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Noncoding RNAs (ncRNAs), in the form of structural, catalytic or regulatory RNAs, have emerged to be critical effectors of many biological processes. With the advent of new technologies, we have begun to appreciate how intracellular and circulatory ncRNAs elegantly choreograph the regulation of gene expression and protein function(s) in the cell. Armed with this knowledge, the clinical utility of ncRNAs as biomarkers has been recently tested in a wide range of human diseases. In this review, we examine how critical factors govern the success of interrogating ncRNA biomarker expression in liquid biopsies and tissues to enhance our current clinical management of human diseases, particularly in the context of cancer. We also discuss strategies to overcome key challenges that preclude ncRNAs from becoming standard-of-care clinical biomarkers, including sample pre-analytics standardization, data cross-validation with closer attention to discordant findings, as well as correlation with clinical outcomes. Although harnessing multi-modal information from disease-associated noncoding RNome (ncRNome) in biofluids or in tissues using artificial intelligence or machine learning is at the nascent stage, it will undoubtedly fuel the community adoption of precision population health.
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Cantarella, Simona, Elena Di Nisio, Davide Carnevali, Giorgio Dieci, and Barbara Montanini. "Interpreting and integrating big data in non-coding RNA research." Emerging Topics in Life Sciences 3, no. 4 (July 30, 2019): 343–55. http://dx.doi.org/10.1042/etls20190004.
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Abstract In the last two decades, we have witnessed an impressive crescendo of non-coding RNA studies, due to both the development of high-throughput RNA-sequencing strategies and an ever-increasing awareness of the involvement of newly discovered ncRNA classes in complex regulatory networks. Together with excitement for the possibility to explore previously unknown layers of gene regulation, these advancements led to the realization of the need for shared criteria of data collection and analysis and for novel integrative perspectives and tools aimed at making biological sense of very large bodies of molecular information. In the last few years, efforts to respond to this need have been devoted mainly to the regulatory interactions involving ncRNAs as direct or indirect regulators of protein-coding mRNAs. Such efforts resulted in the development of new computational tools, allowing the exploitation of the information spread in numerous different ncRNA data sets to interpret transcriptome changes under physiological and pathological cell responses. While experimental validation remains essential to identify key RNA regulatory interactions, the integration of ncRNA big data, in combination with systematic literature mining, is proving to be invaluable in identifying potential new players, biomarkers and therapeutic targets in cancer and other diseases.
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Song, Jijun, and Mingxin Song. "Identification of hydatidosis-related modules and key regulatory genes." PeerJ 8 (June 18, 2020): e9280. http://dx.doi.org/10.7717/peerj.9280.
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Background Echinococcosis caused by larval of Echinococcus is prevalent all over the world. Although clinical experience showed that the presence of tapeworms could not be found in liver lesions, the repeated infection and aggravation of lesions still occur in the host. Here, this study constructed a multifactor-driven disease-related dysfunction network to explore the potential molecular pathogenesis mechanism in different hosts after E.multilocularis infection. Method First, iTRAQ sequencing was performed on human liver infected with E.multilocularis. Second, obtained microRNAs(miRNAs) expression profiles of humans and canine infected with Echinococcus from the GEO database. In addition, we also performed differential expression analysis, protein interaction network analysis, enrichment analysis, and crosstalk analysis to obtain genes and modules related to E.multilocularis infection. Pivot analysis is used to calculate the potential regulatory effects of multiple factors on the module and identify related non-coding RNAs(ncRNAs) and transcription factors(TFs). Finally, we screened the target genes of miRNAs of Echinococcus to further explore its infection mechanism. Results A total of 267 differentially expressed proteins from humans and 3,635 differentially expressed genes from canine were obtained. They participated in 16 human-related dysfunction modules and five canine-related dysfunction modules, respectively. Both human and canine dysfunction modules are significantly involved in BMP signaling pathway and TGF-beta signaling pathway. In addition, pivot analysis found that 1,129 ncRNAs and 110 TFs significantly regulated human dysfunction modules, 158 ncRNAs and nine TFs significantly regulated canine dysfunction modules. Surprisingly, the Echinococcus miR-184 plays a role in the pathogenicity regulation by targeting nine TFs and one ncRNA in humans. Similarly, miR-184 can also cause physiological dysfunction by regulating two transcription factors in canine. Conclusion The results show that the miRNA-184 of Echinococcus can regulate the pathogenic process through various biological functions and pathways. The results laid a solid theoretical foundation for biologists to further explore the pathogenic mechanism of Echinococcosis.
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Zhang, Peijing, Wenyi Wu, Qi Chen, and Ming Chen. "Non-Coding RNAs and their Integrated Networks." Journal of Integrative Bioinformatics 16, no. 3 (July 13, 2019). http://dx.doi.org/10.1515/jib-2019-0027.
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AbstractEukaryotic genomes are pervasively transcribed. Besides protein-coding RNAs, there are different types of non-coding RNAs that modulate complex molecular and cellular processes. RNA sequencing technologies and bioinformatics methods greatly promoted the study of ncRNAs, which revealed ncRNAs’ essential roles in diverse aspects of biological functions. As important key players in gene regulatory networks, ncRNAs work with other biomolecules, including coding and non-coding RNAs, DNAs and proteins. In this review, we discuss the distinct types of ncRNAs, including housekeeping ncRNAs and regulatory ncRNAs, their versatile functions and interactions, transcription, translation, and modification. Moreover, we summarize the integrated networks of ncRNA interactions, providing a comprehensive landscape of ncRNAs regulatory roles.
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Bian, Xingbo, Pengcheng Yu, Ling Dong, Yan Zhao, He Yang, Yongzhong Han, and Lianxue Zhang. "Regulatory role of non-coding RNA in ginseng rusty root symptom tissue." Scientific Reports 11, no. 1 (April 28, 2021). http://dx.doi.org/10.1038/s41598-021-88709-3.
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AbstractGinseng rusty root symptom (GRS) is one of the primary diseases of ginseng. It leads to a severe decline in the quality of ginseng and significantly affects the ginseng industry. The regulatory mechanism of non-coding RNA (ncRNA) remains unclear in the course of disease. This study explored the long ncRNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) in GRS tissues and healthy ginseng (HG) tissues and performed functional enrichment analysis of the screened differentially expressed ncRNAs. Considering the predictive and regulatory effects of ncRNAs on mRNAs, we integrated ncRNA and mRNA data to analyze and construct relevant regulatory networks. A total of 17,645 lncRNAs, 245 circRNAs, and 299 miRNAs were obtained from HG and GRS samples, and the obtained ncRNAs were characterized, including the classification of lncRNAs, length and distribution of circRNA, and the length and family affiliations of miRNAs. In the analysis of differentially expressed ncRNA target genes, we found that lncRNAs may be involved in the homeostatic process of ginseng tissues and that lncRNAs, circRNAs, and miRNAs are involved in fatty acid-related regulation, suggesting that alterations in fatty acid-related pathways may play a key role in GRS. Besides, differentially expressed ncRNAs play an essential role in regulating transcriptional translation processes, primary metabolism such as starch and sucrose, and secondary metabolism such as alkaloids in ginseng tissues. Finally, we integrated the correlations between ncRNAs and mRNAs, constructed corresponding interaction networks, and identified ncRNAs that may play critical roles in GRS. These results provide a basis for revealing GRS's molecular mechanism and enrich our understanding of ncRNAs in ginseng.
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Wang, Mengyao, and Jianbo Wang. "Non-coding RNA expression analysis revealed the molecular mechanism of flag leaf heterosis in inter-subspecific hybrid rice." Frontiers in Plant Science 13 (September 26, 2022). http://dx.doi.org/10.3389/fpls.2022.990656.
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Heterosis has been used widespread in agriculture, but its molecular mechanism is inadequately understood. Plants have a large number of non-coding RNAs (ncRNAs), among them, functional ncRNAs that have been studied widely containing long non-coding RNA (lncRNA) and circular RNA (circRNA) that play a role in varied biological processes, as well as microRNA (miRNA), which can not only regulate the post-transcriptional expression of target genes, but also target lncRNA and circRNA then participate the competing endogenous RNA (ceRNA) regulatory network. However, the influence of these three ncRNAs and their regulatory relationships on heterosis is unknown in rice. In this study, the expression profile of ncRNAs and the ncRNA regulatory network related to heterosis were comprehensively analyzed in inter-subspecific hybrid rice. A total of 867 miRNAs, 3,278 lncRNAs and 2,521 circRNAs were identified in the hybrid and its parents. Analysis of the global profiles of these three types of ncRNAs indicated that significant differences existed in the distribution and sequence characteristics of the corresponding genes. The numbers of miRNA and lncRNA in hybrid were higher than those in its parents. A total of 784 ncRNAs (169 miRNAs, 573 lncRNAs and 42 circRNAs) showed differentially expressed in the hybrid, and their target/host genes were vital in stress tolerance, growth and development in rice. These discoveries suggested that the expression plasticity of ncRNA has an important role of inter-subspecific hybrid rice heterosis. It is worth mentioning that miRNAs exhibited substantially more variations between hybrid and parents compared with observed variation for lncRNA and circRNA. Non-additive expression ncRNAs and allele-specific expression genes-related ncRNAs in hybrid were provided in this study, and multiple sets of ncRNA regulatory networks closely related to heterosis were obtained. Meanwhile, heterosis-related regulatory networks of ceRNA (lncRNA and circRNA) and miRNA were also demonstrated.
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Wang, Erming, Mariana Lemos Duarte, Lauren E. Rothman, Dongming Cai, and Bin Zhang. "Non-coding RNAs and Alzheimer’s disease: perspectives from omics studies." Human Molecular Genetics, August 22, 2022. http://dx.doi.org/10.1093/hmg/ddac202.
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Abstract Neurodegenerative diseases such as Alzheimer’s disease (AD) are characterized by the progressive loss of neurons in the brain and the spinal cord. The pathophysiology of AD is multifactorial with heterogeneous molecular manifestations. The lack of efficacious therapies for AD reinforces the importance of exploring in depth multifaceted disease mechanisms. Recent progresses on AD have generated a large amount of RNA-sequencing data at both bulk and single cell levels and revealed thousands of genes with expression changes in AD. However, the upstream regulators of such gene expression changes are largely unknown. Noncoding RNAs (ncRNAs) represent the majority of the human transcriptome and regulatory ncRNAs have been found to play an important role in regulating gene expression. A single miRNA usually targets a number of mRNAs and thus such ncRNAs are particular important for understanding disease mechanisms and developing novel therapeutics. This review aims to summarize the recent findings on the relevance and the roles of ncRNAs in AD from ncRNA-omics studies with a focus on ncRNA signatures, interactions between ncRNAs and mRNAs, and ncRNA-regulated pathways in AD. We also review the potential of specific ncRNAs to serve as biomarkers and therapeutic targets for AD. In the end, we point out future directions for studying ncRNAs in AD.
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Cai, Zongyan, Shuo Li, Tianci Yu, Jiahui Deng, Xinran Li, and Jiaxin Jin. "Non-Coding RNA Regulatory Network in Ischemic Stroke." Frontiers in Neurology 13 (March 3, 2022). http://dx.doi.org/10.3389/fneur.2022.820858.
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Stroke is a worldwide public health problem that has caused a substantial economic burden to families and society. Despite recent major advances, there is still a need for more timely, effective diagnosis and treatment methods for acute ischemic stroke. Non-coding RNAs (ncRNAs), which widely exist in the human body, do not encode proteins. Instead, these mediate various cellular processes as functional regulatory molecules from the RNA level. Each ncRNA node in organisms is not isolated but constitutes a complex regulatory network, regulating multiple molecular targets and triggering specific physiological or pathological reactions, leading to different outcomes. Abundant studies have proclaimed the impact of ncRNAs in ischemic stroke, which may enlighten new inspirations for diagnosing and treating ischemic stroke. This paper outlines the current understanding of the ncRNA regulatory network and reviews the recent evidence for the contribution of ncRNAs in the experimental ischemic stroke model.