Academic literature on the topic 'MiRNA target'
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Journal articles on the topic "MiRNA target"
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Li, Peng, Yi Chen, Conslata Awino Juma, Chengyong Yang, Jinfeng Huang, Xiaoxiao Zhang, and Yan Zeng. "Differential Inhibition of Target Gene Expression by Human microRNAs." Cells 8, no. 8 (July 30, 2019): 791. http://dx.doi.org/10.3390/cells8080791.
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microRNAs (miRNAs) exert their functions by repressing the expression of their target genes, but most miRNA target genes are unknown, and the degree to which a miRNA differentially inhibits the expression of its targets is underappreciated. We selected human miR-1, miR-122, and miR-124 as representatives to investigate the reliability of miRNA target predictions and examine how miRNAs suppress their targets. We constructed miRNA target gene reporter libraries based on prediction programs TargetScan, miRanda, and PicTar, and performed large-scale reporter assays to directly evaluate whether and how strongly a predicted target gene is repressed by its miRNA. We then performed statistical analyses to examine parameters that contributed to the miRNA inhibition of target genes. We found that the three programs have approximately 72–85% success rates in predicting genuine targets and that the miRNA inhibition of different targets varies in extent. We also identified parameters that could predict the degrees of miRNA repression, and further showed that differential miR-124 repression might contribute to differential gene expression in vivo. Our studies systematically investigated hundreds of miRNA target genes, shed light on factors influencing miRNA functions, and suggested a new mechanism by which differential target repression by miRNAs regulates endogenous gene expression.
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Komatsu, Shintaro, Hiroki Kitai, and Hiroshi I. Suzuki. "Network Regulation of microRNA Biogenesis and Target Interaction." Cells 12, no. 2 (January 13, 2023): 306. http://dx.doi.org/10.3390/cells12020306.
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MicroRNAs (miRNAs) are versatile, post-transcriptional regulators of gene expression. Canonical miRNAs are generated through the two-step DROSHA- and DICER-mediated processing of primary miRNA (pri-miRNA) transcripts with optimal or suboptimal features for DROSHA and DICER cleavage and loading into Argonaute (AGO) proteins, whereas multiple hairpin-structured RNAs are encoded in the genome and could be a source of non-canonical miRNAs. Recent advances in miRNA biogenesis research have revealed details of the structural basis of miRNA processing and cluster assistance mechanisms that facilitate the processing of suboptimal hairpins encoded together with optimal hairpins in polycistronic pri-miRNAs. In addition, a deeper investigation of miRNA–target interaction has provided insights into the complexity of target recognition with distinct outcomes, including target-mediated miRNA degradation (TDMD) and cooperation in target regulation by multiple miRNAs. Therefore, the coordinated or network regulation of both miRNA biogenesis and miRNA–target interaction is prevalent in miRNA biology. Alongside recent advances in the mechanistic investigation of miRNA functions, this review summarizes recent findings regarding the ordered regulation of miRNA biogenesis and miRNA–target interaction.
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Chen, Yuhao, and Xiaowei Wang. "miRDB: an online database for prediction of functional microRNA targets." Nucleic Acids Research 48, no. D1 (August 31, 2019): D127—D131. http://dx.doi.org/10.1093/nar/gkz757.
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Abstract MicroRNAs (miRNAs) are small noncoding RNAs that act as master regulators in many biological processes. miRNAs function mainly by downregulating the expression of their gene targets. Thus, accurate prediction of miRNA targets is critical for characterization of miRNA functions. To this end, we have developed an online database, miRDB, for miRNA target prediction and functional annotations. Recently, we have performed major updates for miRDB. Specifically, by employing an improved algorithm for miRNA target prediction, we now present updated transcriptome-wide target prediction data in miRDB, including 3.5 million predicted targets regulated by 7000 miRNAs in five species. Further, we have implemented the new prediction algorithm into a web server, allowing custom target prediction with user-provided sequences. Another new database feature is the prediction of cell-specific miRNA targets. miRDB now hosts the expression profiles of over 1000 cell lines and presents target prediction data that are tailored for specific cell models. At last, a new web query interface has been added to miRDB for prediction of miRNA functions by integrative analysis of target prediction and Gene Ontology data. All data in miRDB are freely accessible at http://mirdb.org.
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Mohebbi, Mohammad, Liang Ding, Russell L. Malmberg, Cory Momany, Khaled Rasheed, and Liming Cai. "Accurate prediction of human miRNA targets via graph modeling of the miRNA-target duplex." Journal of Bioinformatics and Computational Biology 16, no. 04 (August 2018): 1850013. http://dx.doi.org/10.1142/s0219720018500130.
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miRNAs are involved in many critical cellular activities through binding to their mRNA targets, e.g. in cell proliferation, differentiation, death, growth control, and developmental timing. Accurate prediction of miRNA targets can assist efficient experimental investigations on the functional roles of miRNAs. Their prediction, however, remains a challengeable task due to the lack of experimental data about the tertiary structure of miRNA-target binding duplexes. In particular, correlations of nucleotides in the binding duplexes may not be limited to the canonical Watson Crick base pairs (BPs) as they have been perceived; methods based on secondary structure prediction (typically minimum free energy (MFE)) have only had mix success. In this work, we characterized miRNA binding duplexes with a graph model to capture the correlations between pairs of nucleotides of an miRNA and its target sequences. We developed machine learning algorithms to train the graph model to predict the target sites of miRNAs. In particular, because imbalance between positive and negative samples can significantly deteriorate the performance of machine learning methods, we designed a novel method to re-sample available dataset to produce more informative data learning process. We evaluated our model and miRNA target prediction method on human miRNAs and target data obtained from mirTarBase, a database of experimentally verified miRNA-target interactions. The performance of our method in target prediction achieved a sensitivity of 86% with a false positive rate below 13%. In comparison with the state-of-the-art methods miRanda and RNAhybrid on the test data, our method outperforms both of them by a significant margin. The source codes, test sets and model files all are available at http://rna-informatics.uga.edu/?f=software&p=GraB-miTarget .
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Liu, Chun-Jie, Xin Fu, Mengxuan Xia, Qiong Zhang, Zhifeng Gu, and An-Yuan Guo. "miRNASNP-v3: a comprehensive database for SNPs and disease-related variations in miRNAs and miRNA targets." Nucleic Acids Research 49, no. D1 (September 29, 2020): D1276—D1281. http://dx.doi.org/10.1093/nar/gkaa783.
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Abstract MicroRNAs (miRNAs) related single-nucleotide variations (SNVs), including single-nucleotide polymorphisms (SNPs) and disease-related variations (DRVs) in miRNAs and miRNA-target binding sites, can affect miRNA functions and/or biogenesis, thus to impact on phenotypes. miRNASNP is a widely used database for miRNA-related SNPs and their effects. Here, we updated it to miRNASNP-v3 (http://bioinfo.life.hust.edu.cn/miRNASNP/) with tremendous number of SNVs and new features, especially the DRVs data. We analyzed the effects of 7 161 741 SNPs and 505 417 DRVs on 1897 pre-miRNAs (2630 mature miRNAs) and 3′UTRs of 18 152 genes. miRNASNP-v3 provides a one-stop resource for miRNA-related SNVs research with the following functions: (i) explore associations between miRNA-related SNPs/DRVs and diseases; (ii) browse the effects of SNPs/DRVs on miRNA-target binding; (iii) functional enrichment analysis of miRNA target gain/loss caused by SNPs/DRVs; (iv) investigate correlations between drug sensitivity and miRNA expression; (v) inquire expression profiles of miRNAs and their targets in cancers; (vi) browse the effects of SNPs/DRVs on pre-miRNA secondary structure changes; and (vii) predict the effects of user-defined variations on miRNA-target binding or pre-miRNA secondary structure. miRNASNP-v3 is a valuable and long-term supported resource in functional variation screening and miRNA function studies.
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Praher, Daniela, Bob Zimmermann, Rohit Dnyansagar, David J. Miller, Aurelie Moya, Vengamanaidu Modepalli, Arie Fridrich, et al. "Conservation and turnover of miRNAs and their highly complementary targets in early branching animals." Proceedings of the Royal Society B: Biological Sciences 288, no. 1945 (February 24, 2021): 20203169. http://dx.doi.org/10.1098/rspb.2020.3169.
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MicroRNAs (miRNAs) are crucial post-transcriptional regulators that have been extensively studied in Bilateria, a group comprising the majority of extant animals, where more than 30 conserved miRNA families have been identified. By contrast, bilaterian miRNA targets are largely not conserved. Cnidaria is the sister group to Bilateria and thus provides a unique opportunity for comparative studies. Strikingly, like their plant counterparts, cnidarian miRNAs have been shown to predominantly have highly complementary targets leading to transcript cleavage by Argonaute proteins. Here, we assess the conservation of miRNAs and their targets by small RNA sequencing followed by miRNA target prediction in eight species of Anthozoa (sea anemones and corals), the earliest-branching cnidarian class. We uncover dozens of novel miRNAs but only a few conserved ones. Further, given their high complementarity, we were able to computationally identify miRNA targets in each species. Besides evidence for conservation of specific miRNA target sites, which are maintained between sea anemones and stony corals across 500 Myr of evolution, we also find indications for convergent evolution of target regulation by different miRNAs. Our data indicate that cnidarians have only few conserved miRNAs and corresponding targets, despite their high complementarity, suggesting a high evolutionary turnover.
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ZHENG, YUN, and WEIXIONG ZHANG. "ANIMAL MICRORNA TARGET PREDICTION USING DIVERSE SEQUENCE-SPECIFIC DETERMINANTS." Journal of Bioinformatics and Computational Biology 08, no. 04 (August 2010): 763–88. http://dx.doi.org/10.1142/s0219720010004896.
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Many recent studies have shown that access of animal microRNAs (miRNAs) to their complementary sites in target mRNAs is determined by several sequence-specific determinants beyond the seed regions in the 5′ end of miRNAs. These factors have been related to the repressive power of miRNAs and used in some programs to predict the efficacy of miRNA complementary sites. However, these factors have not been systematically examined regarding their capacities for improving miRNA target prediction. We develop a new miRNA target prediction algorithm, called Hitsensor, by incorporating many sequence-specific features that determine complementarities between miRNAs and their targets, in addition to the canonical seed regions in the 5′ ends of miRNAs. We evaluate the performance of our algorithm on 720 known animal miRNA:target pairs in four species, Homo sapiens, Mus musculus, Drosophila melanogaster and Caenorhabditis elegans. Our experimental results show that Hitsensor outperforms five popular existing algorithms, indicating that our unique scheme for quantifying the determinants of complementary sites is effective in improving the performance of a miRNA target prediction algorithm. We also examine the effectiveness of miRNA-mediated repression for the predicted targets by using a published quantitative protein expression dataset of miR-223 knockout in mouse neutrophils. Hitsensor identifies more targets than the existing algorithms, and the predicted targets of Hitsensor show comparable protein level changes to those of the existing algorithms.
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McGeary, Sean E., Kathy S. Lin, Charlie Y. Shi, Thy M. Pham, Namita Bisaria, Gina M. Kelley, and David P. Bartel. "The biochemical basis of microRNA targeting efficacy." Science 366, no. 6472 (December 5, 2019): eaav1741. http://dx.doi.org/10.1126/science.aav1741.
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MicroRNAs (miRNAs) act within Argonaute proteins to guide repression of messenger RNA targets. Although various approaches have provided insight into target recognition, the sparsity of miRNA-target affinity measurements has limited understanding and prediction of targeting efficacy. Here, we adapted RNA bind-n-seq to enable measurement of relative binding affinities between Argonaute-miRNA complexes and all sequences ≤12 nucleotides in length. This approach revealed noncanonical target sites specific to each miRNA, miRNA-specific differences in canonical target-site affinities, and a 100-fold impact of dinucleotides flanking each site. These data enabled construction of a biochemical model of miRNA-mediated repression, which was extended to all miRNA sequences using a convolutional neural network. This model substantially improved prediction of cellular repression, thereby providing a biochemical basis for quantitatively integrating miRNAs into gene-regulatory networks.
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ALKANLI, Nevra, and Arzu AY. "Kanser Gelişimi ve Progresyonunda miRNA’LAR VE miRNA Gen Varyasyonları." Gevher Nesibe Journal IESDR 6, no. 13 (July 25, 2021): 38–45. http://dx.doi.org/10.46648/gnj.226.
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MicroRNAs (miRNAs) are short non-coding RNA class and perform regulatory functions at the post transcriptional level as tumor suppressors or oncogenes. miRNAs are effective in cell differentiation, cell proliferation and apoptosis regulation in normal development processes. miRNA gene variations associated with gene silencing mechanisms, , pri-miRNA, pre-miRNA, mat-miRNA gene variations, genetic cariations in target sites of miRNAs have been identified. Significant changes may occur in miRNA expression levels as a result of genetic variations defined in miRNA genes. Therefore, it is thought that genetic variations in miRNA genes may be biomarkers that can play an important role in cancer formation, prognosis and progression. MiRNA function disorder due to miRNA-mediated dysregulation in target genes that may occur as a result of miRNA gene variations in the diagnosis and progression of various types of cancer should be evaluated. In addition, determining miRNAs and miRNA gene variations in target genes that affect drug behavior in increasing the effectiveness of drugs is very important in terms of developing new treatment methods and different therapeutic strategies for various cancer types. In this review, it is aimed to examine the potential roles of miRNAs and miRNA gene variations in cancer development, progression and treatment.
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Chen, Jiajia, and Liangzhi Li. "Multiple Regression Analysis Reveals MicroRNA Regulatory Networks in Oryza sativa under Drought Stress." International Journal of Genomics 2018 (October 4, 2018): 1–12. http://dx.doi.org/10.1155/2018/9395261.
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Drought is a major abiotic stress that reduces rice development and yield. miRNAs (microRNAs) are known to mediate posttranscriptional regulation under drought stress. Although the importance of individual miRNAs has been established, the crosstalks between miRNAs and mRNAs remain unearthed. Here we performed microarray analysis of miRNAs and matched mRNA expression profiles of drought-treated rice cultivar Nipponbare. Drought-responsive miRNA-mRNA regulations were identified by a combination of a partial least square (PLS) regression approach and sequence-based target prediction. A drought-induced network with 13 miRNAs and 58 target mRNAs was constructed, and four miRNA coregulatory modules were revealed. Functional analysis suggested that drought-response miRNA targets are enriched in hormone signaling, lipid and carbohydrate metabolism, and antioxidant defense. 13 candidate miRNAs and target genes were validated by RT-qPCR, hierarchical clustering, and ROC analysis. Two target genes (DWARF-3 and P0651G05.2) of miRNA coregulatory modules were further verified by RLM-5′ RACE. Together, our integrative study of miRNA-mRNA interaction provided attractive candidates that will help elucidate the drought-response mechanisms in Oryza sativa.
Dissertations / Theses on the topic "MiRNA target"
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Gebhardt, Marie Luise. "Enrichment of miRNA targets in REST-regulated genes allows filtering of miRNA target predictions." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17407.
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Vorhersagen von miRNA-Bindestellen enthalten oft einen hohen Prozentsatz an falsch positiven Ergebnissen (24-70%). Gleichzeitig ist es schwierig die biologischen Interaktionen von miRNAs und ihren Zieltranskripten auf experimentellem Wege und Genom weit zu messen. Daher wurde in der vorliegenden Arbeit die Frage beantwortet, ob ChIP-Sequenzierungsdaten, von denen es immer mehr gibt, verwendet werden können, um Vorhersagen von miRNA-Bindestellen zu filtern. Dabei wurde von einem Netzwerk aus miRNAs und Transkriptionsfaktoren gebraucht gemacht, die Zieltranskripte gemeinsam regulieren. Zunächst wurden verschiedene Methoden getestet, mit denen „Peaks“ aus der ChIP-Sequenzierung Zielgenen zugeordnet werden können. Zielgenlisten des transkriptionalen Repressors RE1-silencing transcription factor (REST/NRSF) wurden mithilfe von ChIP-Sequenzierungsdaten erzeugt. Ein Algorithmus zur Suche nach überrepräsentierten miRNA-Zielgenen in REST-Genlisten basierend auf Vorhersagen von TargetScanHuman wurde entwickelt und angewandt. Die detektierten „enrichment“-miRNAs waren Teil eines vielfältig regulierten REST-miRNA-Netzwerks. Mögliche Funktionen von miRNAs wurden vorgeschlagen und ihre Rolle im gemeinsamen Netzwerk mit REST und im damit gebildeten Netzwerkmotiv (Inkoherente Schleife zur Vorwärtskopplung Typ 2) wurde analysiert. Es stellte sich heraus, dass ein Filtern der Vorhersagen tatsächlich möglich ist, da Gene, die sowohl von REST als auch von einer oder mehreren „enrichment“-miRNAs reguliert werden, einen höheren Anteil an wahren miRNA-Transkript-Interaktionen haben.Predictions of miRNA binding sites suffer from high false positive rates (24-70%) and measuring biological interactions of miRNAs and target transcripts on a genome wide scale remains challenging. In the thesis at hand the question was answered if the ever growing body of ChIP-sequencing data can be applied to filter miRNA target predictions by making use of the underlying regulatory network of miRNAs and transcription factors. First different methods for association of ChIP-sequencing peaks to target genes were tested. Target gene lists of the transcriptional repressor RE1-silencing transcription factor (REST/NRSF) were generated by means of ChIP-sequencing data. An enrichment analysis tool based on predictions from TargetScanHuman was developed and applied to find ‘enrichment’-miRNAs with over-represented targets in the REST gene lists. The detected miRNAs were shown to be part of a highly regulated REST-miRNA network. Possible functions could be assigned to them and their role in the regulatory network and special network motifs (incoherent feedforward loop of type 2) was analyzed. It turned out that miRNA target predictions of genes shared by enrichment-miRNAs and REST had a higher proportion of true positive associations than the TargetScanHuman background, thus the procedure made a filtering possible.
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Bitetti, Angelo. "MiRNA degradation by a conserved target RNA regulates animal behavior." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066276.
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L’objectif de mon projet principal de thèse est de déterminer la fonction biologique d’un lncARN conservés chez le zebrafish que nous avons appelé libra. La séquence de libra étant hautement homologue à la région 3’UTR de la protéine Nrep. Ces deux transcrits, libra et Nrep, contiennent en effet un site de liaison au miARN profondément conservé et inhabituellement complémentaire au miR-29. En utilisant à le modèle souris et les cellules murines, nous avons décrypté la relation régulatrice entre ce transcrit conservé dans l’évolution des vertébrés et la voie métabolique des miARN. Nous avons montré que Nrep limite le domaine d’expression de miR-29 au cervelet, et qu’il le déstabilise en rognant sa séquence. Notre travail révèle donc le premier exemple de dégradation endogène ciblée des miARN (ou TDMD). De plus, un ensemble d’expériences in vivo sur les modèles zebrafish et souris, nous a permis de démontrer que libra et Nrep contrôlent tout les deux le comportement animal. Via la perturbation génétique du site de liaison au miARN de Nrep murin, nous avons observé que ce gène régule le dosage du miR29 de part son site de liaison aux miARN, et que cette régulation est nécessaire à un comportement animal normal. Dans la seconde partie de ma thèse, je décris une stratégie exploré afin de déréguler les lncARN de la manière la moins invasive possible. Les lncARN sont actuellement neutralisés par des approches qui introduisent de vastes changements de séquence au niveau génomique. Nous avons donc développer une stratégie in vivo, appliquée au zebrafish, qui inactive les lncARN via l’insertion génomique d’une séquence ribozyme autoclivante ou d’un signal polyA prématuréThe goal of my main thesis project was to determine the biological function of a deeply conserved zebrafish long noncoding RNAs (lncRNA) which we called libra. libra shows sequence similarity with the 3'UTR of the NREP a protein coding transcript. Both libra and Nrep contain a deeply conserved and unusually complementary microRNA (miRNA) binding site for miR-29. Using both the mouse model and mouse cell lines, we deciphered the regulatory relationship between this conserved transcript and the miRNA pathway. We showed that Nrep restricts the spatial expression domain of miR-29 in the cerebellum and that it destabilizes miR-29 through 3' trimming. Until now, only viral transcripts and artificial reporters engineered to contain highly complementary miRNA binding sites have been shown to regulate miRNAs in this fashion. Thus, our work uncovers the first example of endogenous target-directed miRNA degradation (TDMD). In addition, through a set of in vivo experiments in zebrafish and mouse, we showed that both libra and Nrep control normal animal behavior. By genetically disrupting the miR-29 binding site in Nrep in mouse, we showed that Nrep regulates miR-29 dosage through its miR-29 site and controls animal behavioral. In a second part of my thesis I describe a strategy to genetically downregulate lncRNAs in a minimally invasive manner. Approaches to knock-out lncRNAs that do not introduce vast sequence changes at the genomic level have not been adequately developed yet. I present our in vivo strategy applied to the zebrafish model using a genomic knock-in of a self-cleaving ribozyme sequence and a premature poly(A) signal to knock-out lncRNAs
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Gebhardt, Marie Luise [Verfasser], Uwe [Akademischer Betreuer] Ohler, Miguel [Akademischer Betreuer] Andrade, and Ana [Akademischer Betreuer] Pombo. "Enrichment of miRNA targets in REST-regulated genes allows filtering of miRNA target predictions / Marie Luise Gebhardt. Gutachter: Uwe Ohler ; Miguel Andrade ; Ana Pombo." Berlin : Lebenswissenschaftliche Fakultät, 2016. http://d-nb.info/108141846X/34.
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Gebhardt, Marie [Verfasser], Uwe [Akademischer Betreuer] Ohler, Miguel [Akademischer Betreuer] Andrade, and Ana [Akademischer Betreuer] Pombo. "Enrichment of miRNA targets in REST-regulated genes allows filtering of miRNA target predictions / Marie Luise Gebhardt. Gutachter: Uwe Ohler ; Miguel Andrade ; Ana Pombo." Berlin : Lebenswissenschaftliche Fakultät, 2016. http://d-nb.info/108141846X/34.
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Frampton, Adam. "The complex network of miRNA and mRNA target interactions in pancreatic cancer." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/24951.
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Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is one of the most lethal tumour types world-wide. The majority of patients present late with locally advanced or metastatic disease. Therefore, despite advances in operative techniques, perioperative management and oncological treatments, the overall 5-year survival remains <5%. Determining tumoural factors that contribute towards its aggressive nature may help in identifying novel molecular biomarkers and/or therapeutic targets. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate target gene expression and are able to act as tumour suppressors or oncogenes. MiRNAs have been extensively profiled and implicated in the initiation and progression of PDAC. Furthermore, there is a possibility of translating miRNAs into clinically useful biomarkers. Here, I developed upon these initial observations and demonstrate that miRNAs can be used to differentiate low risk pancreatic benign cystic tumours (BCTs) from PDAC. We confirmed that these miRNAs regulate the expression of known PDAC oncogenes, and that miR-16, miR-126 and let-7d target BCL2, CRK and KRAS respectively. Next, in order to investigate the main contributors to tumourigenesis, an integrated molecular analysis (miRNA-mRNA) was performed in PDAC. By using a combination of network-based bioinformatics, miR-21, miR-23a and miR-27a were prioritised as important in PDAC progression. We demonstrated that the use of a combination of miRNA inhibitors (against miR-21, miR-23a and miR-27a) in a murine subcutaneous PDAC xenograft model was able to reduce tumour growth, better than oncomiR-21 inhibition alone. BTG2 and NEDD4L were found to be direct targets of the miRNA combination and were established as new candidate tumour suppressors in PDAC. The clinical relevance of this 3 miRNA signature was demonstrated, as high expressors of the combination have poor overall survival after surgical resection, independent of other clinicopathologic factors. Together, these studies identify specific miRNAs as important regulators of PDAC tumourigenesis and their possible use as biomarkers.
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Bosson, Andrew D. (Andrew David). "Modulation of Ago-miRNA regulatory networks by cis-sequence elements and target competition." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/89938.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2014.Vita. Cataloged from PDF version of thesis.
Includes bibliographical references.
regulators of gene expression in a wide range of organisms and biological processes. Each miRNA guides Argonaute (Ago) protein complexes to target and repress hundreds of genes in a sequence-dependent manner. To identify all targets of miRNA regulation, we performed UV crosslinking and immunoprecipitation (CLIP) of Ago complexes in mouse embryonic (ESC) and mesenchymal (MSC) stem cell lines. We also captured the genome-wide miRNA-independent binding footprint of Ago by performing CLIP in cells that lack Dicer, an enzyme required for mature miRNA biogenesis. We surprisingly found that Ago bound a similar set of genes in the absence of Dicer, and this overlap in target genes was due partially to residual, unprocessed miRNAs in the Dicer KO cells. Other potential sites of miRNA-independent Ago interactions, such as histone transcripts and poly-A cleavage and polyadenylation sites, were also identified. One Ago CLIP dataset revealed the enrichment for a G-rich sequence motif at Ago target sites. We later demonstrated that the G-motif is not directly bound to Ago but rather is enriched near miRNA-guided Ago binding sites. Its presence near miRNA target sites is associated with stronger repression of Ago-miRNA targets. Fortuitously, the original Ago CLIP dataset that identified the G-motif was later shown to likely contain target sites of another co-immunoprecipitating RNA binding protein (RBP). Using mass spectroscopy of Ago antibody immunoprecipitations from Ago KO cells, we identified a list of interacting RBPs that could potentially augment Ago-miRNA activity through the G-motif. To investigate target competition in miRNA networks, we related our CLIP analysis of genome-wide, quantitative Ago binding to measurements of absolute miRNA and target RNA concentrations. We found that all miRNAs other than the miR-290 family in ESCs and let-7 family in MSCs were expressed at concentrations below their total target pool. However, 8-12 miRNA families were expressed at near or greater than equimolar ratios with their pool of high affinity targets, and this affinity-partitioned stoichiometry led to significant Ago accumulation and repression of high affinity target sites despite little consequential binding at low affinity sites. Single-cell reporter assays demonstrated that high expressed miRNAs are not susceptible to physiological inductions of competing target transcripts but targets of lower expressed miRNAs are derepressed in a weakly threshold-like manner upon increased target pool levels. In summary, we identify a network of confidently bound targets of miRNA regulation in ESCs and MSCs, reveal the extent of miRNA-independent binding in these two cell types, provide a list of potential miRNA enhancer RBPs, and create a quantitative context for evaluating target competition in miRNA networks.
by Andrew D. Bosson.
Ph. D.
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Warrander, Fiona. "The role of lin28, an FGF signalling target, in development and miRNA regulation." Thesis, University of York, 2012. http://etheses.whiterose.ac.uk/3389/.
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The related genes lin28a and lin28b code for conserved RNA-binding proteins, which contain two key RNA-binding motifs that determine their functions. Previously, our laboratory identified lin28a as a putative downstream target of FGF signalling in the early Xenopus embryo. This was found to occur at gastrulation stage, during which key signalling pathways such as the FGF pathway are active in specifying germ layer development. lin28 is a heterochronic gene in C. elegans and controls the timing of developmental events. In vertebrates, the lin28a gene shows pluripotent-specific expression, and has come to particular interest as one of four factors used to successfully re-program differentiated somatic cells into induced pluripotent stem cells. Both lin28a and lin28b have a high prevalence of ectopic expression in cancer. A well characterised target of both lin28a and lin28b is the microRNA let-7, inhibiting biogenesis to the mature microRNA form. The lin28 proteins have also been shown to potentiate translation of numerous mRNA targets. The aim of this project was to identify if lin28 has an important developmental role in vertebrates. Work in the Xenopus tropicalis embryo found that both lin28a and lin28b were targets of FGF signalling at gastrulation, and were required for correct germ layer patterning at this stage. In order to explore conservation in humans, mesenchymal stem cells were used to model the effects of FGF signalling upon the mesodermal germ layer, and whether lin28 played a role in this. Additional pluripotent cell models were investigated for their suitability in which to study lin28 function. Analysis of lin28 targets in Xenopus revealed that the miR-17-92 cluster family of miRNA may be positively regulated by the lin28 proteins, with a direct interaction possible with a member of these: pre-mir-363. These miRNAs may have further important developmental roles in response to this regulation by the lin28 proteins.
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Reimegård, Johan. "Making Sense of Antisense." Doctoral thesis, Uppsala universitet, Mikrobiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-131168.
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RNA is a highly versatile molecule with functions that span from being a messenger in the transfer from DNA to protein, a catalytic molecule important for key processes in the cell to a regulator of gene expression. The post-genomic era and the use of new techniques to sequence RNAs have dramatically increased the number of regulatory RNAs during the last decade. Many of these are antisense RNAs, as for example the miRNA in eukaryotes and most sRNAs in bacteria. Antisense RNAs bind to specific targets by basepairing and thereby regulate their expression. A major step towards an understanding of the biological role of a miRNA or an sRNA is taken when one identifies which target it regulates. We have used RNA libraries to study the RNA interference pathway during development in the unicellular model organism Dictyostelium discoideum. We have also, by combining computational and experimental methods, discovered the first miRNAs in this organism and shown that they have different expression profiles during development. In parallel, we have developed a novel approach to predict targets for sRNAs in bacteria and used it to discover sRNA/target RNA interactions in the model organism Escherichia coli. We have found evidence for, and further characterized, three of these predicted sRNA/target interactions. For instance, the sRNA MicA is important for regulation of the outer membrane protein OmpA, the sRNAs OmrA and OmrB regulate the transcription factor CsgD, which is important in the sessile lifestyle of E. coli, and MicF regulates its own expression in a feed forward loop via the regulatory protein Lrp. In conclusion, we have discovered novel antisense RNAs, e.g. miRNAs in D. discoideum, developed an approach to identify targets for antisense RNAs, i.e. a target prediction program for sRNAs in bacteria, and verified and characterized some of the predicted antisense RNA interactions.
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Slaibi, Jinani Elias. "Targets of Hsa-miR-488* In Human Prostate Carcinoma Cells." Cleveland State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=csu1273843449.
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Higashi, Susan. "MiRNA and co : methodologically exploring the world of small RNAs." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10252/document.
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La principale contribution de cette thèse est le développement d'une méthode fiable, robuste, et rapide pour la prédiction des pré-miARNs. Deux objectifs avaient été assignés : efficacité et flexibilité. L'efficacité a été rendue possible au moyen d'un algorithme quadratique. La flexibilité repose sur deux aspects, la nature des données expérimentales et la position taxonomique de l'organisme (en particulier plantes ou animaux). Mirinho accepte en entrée des séquences de génomes complets mais aussi les très nombreuses séquences résultant d'un séquençage massif de type NGS de “RNAseq”. “L'universalité” taxonomique est obtenu par la possibilité de modifier les contraintes sur les tailles de la tige (double hélice) et de la boule terminale. Dans le cas de la prédiction des miARN de plantes la plus grande longueur de leur pré-miARN conduit à des méthodes d'extraction de la structure secondaire en tige-boule moins précises. Mirinho prend en compte ce problème lui permettant de fournir des structures secondaires de pré-miARN plus semblables à celles de miRBase que les autres méthodes disponibles. Mirinho a été utilisé dans le cadre de deux questions biologiques précises l'une concernant des RNAseq l'autre de l'ADN génomique. La première question a conduit au traitement et l'analyse des données RNAseq de Acyrthosiphon pisum, le puceron du pois. L'objectif était d'identifier les miARN qui sont différentiellement exprimés au cours des quatre stades de développement de cette espèce et sont donc des candidats à la régulation des gènes au cours du développement. Pour cette analyse, nous avons développé un pipeline, appelé MirinhoPipe. La deuxieme question a permis d'aborder les problèmes liés à la prévision et l'analyse des ARN non-codants (ARNnc) dans la bactérie Mycoplasma hyopneumoniae. Alvinho a été développé pour la prédiction de cibles des miRNA autour d'une segmentation d'une séquence numérique et de la détection de la conservation des séquences entre ncRNA utilisant un graphe k-partite. Nous avons finalement abordé un problème lié à la recherche de motifs conservés dans un ensemble de séquences et pouvant ainsi correspondre à des éléments fonctionnelsThe main contribution of this thesis is the development of a reliable, robust, and much faster method for the prediction of pre-miRNAs. With this method, we aimed mainly at two goals: efficiency and flexibility. Efficiency was made possible by means of a quadratic algorithm. Flexibility relies on two aspects, the input type and the organism clade. Mirinho can receive as input both a genome sequence and small RNA sequencing (sRNA-seq) data of both animal and plant species. To change from one clade to another, it suffices to change the lengths of the stem-arms and of the terminal loop. Concerning the prediction of plant miRNAs, because their pre-miRNAs are longer, the methods for extracting the hairpin secondary structure are not as accurate as for shorter sequences. With Mirinho, we also addressed this problem, which enabled to provide pre-miRNA secondary structures more similar to the ones in miRBase than the other available methods. Mirinho served as the basis to two other issues we addressed. The first issue led to the treatment and analysis of sRNA-seq data of Acyrthosiphon pisum, the pea aphid. The goal was to identify the miRNAs that are expressed during the four developmental stages of this species, allowing further biological conclusions concerning the regulatory system of such an organism. For this analysis, we developed a whole pipeline, called MirinhoPipe, at the end of which Mirinho was aggregated. We then moved on to the second issue, that involved problems related to the prediction and analysis of non-coding RNAs (ncRNAs) in the bacterium Mycoplasma hyopneumoniae. A method, called Alvinho, was thus developed for the prediction of targets in this bacterium, together with a pipeline for the segmentation of a numerical sequence and detection of conservation among ncRNA sequences using a kpartite graph. We finally addressed a problem related to motifs, that is to patterns, that may be composed of one or more parts, that appear conserved in a set of sequences and may correspond to functional elements
Books on the topic "MiRNA target"
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Schmidt, Marco F., ed. Drug Target miRNA. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-6563-2.
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Sethi, Seema. miRNAs and Target Genes in Breast Cancer Metastasis. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-08162-5.
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Schmidt, Marco F. Drug Target MiRNA: Methods and Protocols. Springer New York, 2018.
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Schmidt, Marco F. Drug Target Mirna: Methods and Protocols. Springer New York, 2016.
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Sethi, Seema. miRNAs and Target Genes in Breast Cancer Metastasis. Springer, 2014.
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Sethi, Seema. MiRNAs and Target Genes in Breast Cancer Metastasis. Springer, 2014.
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Reckman, Yolan J., and Yigal M. Pinto. The role of non-coding RNA/microRNAs in cardiac disease. Edited by José Maria Pérez-Pomares, Robert G. Kelly, Maurice van den Hoff, José Luis de la Pompa, David Sedmera, Cristina Basso, and Deborah Henderson. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198757269.003.0031.
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In the past two decades, our knowledge about non-coding DNA has increased tremendously. While non-coding DNA was initially discarded as ‘junk DNA’, we are now aware of the important and often crucial roles of RNA transcripts that do not translate into protein. Non-coding RNAs (ncRNAs) play important functions in normal cellular homeostasis and also in many diseases across all organ systems. Among the different ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been studied the most. In this chapter we discuss the role of miRNAs and lncRNAs in cardiac disease. We present examples of miRNAs with fundamental roles in cardiac development (miR-1), hypertrophy (myomiRs, miR-199, miR-1/133), fibrosis (miR-29, miR-21), myocardial infarction (miR-15, miR17~92), and arrhythmias/conduction (miR-1). We provide examples of lncRNAs related to cardiac hypertrophy (MHRT, CHRF), myocardial infarction (ANRIL, MIAT), and arrhythmias (KCNQ1OT1). We also discuss miRNAs and lncRNAs as potential therapeutic targets or biomarkers in cardiac disease.
Book chapters on the topic "MiRNA target"
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Zhang, Yan. "MiRNA Target." In Encyclopedia of Systems Biology, 1374–75. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4419-9863-7_324.
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Heyn, Jens, Ludwig Christian Hinske, Carola Ledderose, Elisabeth Limbeck, and Simone Kreth. "Experimental miRNA Target Validation." In MicroRNA Protocols, 83–90. Totowa, NJ: Humana Press, 2012. http://dx.doi.org/10.1007/978-1-62703-083-0_7.
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Younger, Scott T., and David R. Corey. "Identification and Validation of miRNA Target Sites Within Nontraditional miRNA Targets." In Methods in Molecular Biology, 53–67. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1369-5_5.
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Fahlgren, Noah, and James C. Carrington. "miRNA Target Prediction in Plants." In Methods in Molecular Biology, 51–57. Totowa, NJ: Humana Press, 2009. http://dx.doi.org/10.1007/978-1-60327-005-2_4.
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Lukasik, Anna, and Piotr Zielenkiewicz. "An Overview of miRNA and miRNA Target Analysis Tools." In Methods in Molecular Biology, 65–87. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9042-9_5.
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Tang, Guiliang, Yu Xiang, Zhensheng Kang, Venugopal Mendu, Xiaohu Tang, Xiaoyun Jia, Qi-Jun Chen, and Xiaoqing Tang. "Small RNA Technologies: siRNA, miRNA, antagomiR, Target Mimicry, miRNA Sponge and miRNA Profiling." In Current Perspectives in microRNAs (miRNA), 17–33. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-8533-8_2.
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Dweep, Harsh, Norbert Gretz, and Carsten Sticht. "miRWalk Database for miRNA–Target Interactions." In RNA Mapping, 289–305. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1062-5_25.
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Rahman, Fazlur, Sajjadul Kadir Akand, Muniba Faiza, Shams Tabrez, and Abdur Rub. "miRNA Target Prediction: Overview and Applications." In Integrated Omics Approaches to Infectious Diseases, 241–53. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-16-0691-5_14.
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Wang, Zhiguo. "Multiple-Target Anti-miRNA Antisense Oligonucleotides Technology." In MicroRNA Interference Technologies, 145–51. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-642-00489-6_8.
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Akhtar, Most Mauluda, Luigina Micolucci, Md Soriful Islam, Fabiola Olivieri, and Antonio Domenico Procopio. "A Practical Guide to miRNA Target Prediction." In Methods in Molecular Biology, 1–13. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9207-2_1.
Full textConference papers on the topic "MiRNA target"
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Zhang, Yanju, Jeroen S. de Bruin, and Fons J. Verbeek. "miRNA target prediction through mining of miRNA relationships." In 2008 8th IEEE International Conference on Bioinformatics and BioEngineering (BIBE). IEEE, 2008. http://dx.doi.org/10.1109/bibe.2008.4696695.
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Mohebbi, Mohammad, Liang Ding, Russell L. Malmberg, Cory Momany, Khaled Rasheed, and Liming Cai. "Accurate prediction of human miRNA targets via graph modeling of miRNA-target duplex." In 2016 IEEE 6th International Conference on Computational Advances in Bio and Medical Sciences (ICCABS). IEEE, 2016. http://dx.doi.org/10.1109/iccabs.2016.7802792.
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Ahmed, Emad E., Sherin M. El-Gokhy, and Mohamed T. Faheem Saidahmed. "Enhanced framework for miRNA target prediction." In 2017 12th International Conference on Computer Engineering and Systems (ICCES). IEEE, 2017. http://dx.doi.org/10.1109/icces.2017.8275367.
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Ning Wang, Yang Wang, Yaodong Yang, Yi Shen, and Ao Li. "miRNA Target Prediction Based on Gene Ontology." In 2013 6th International Symposium on Computational Intelligence and Design (ISCID). IEEE, 2013. http://dx.doi.org/10.1109/iscid.2013.113.
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Zahid, Muhammad Ammar, and Abdelali Agouni. "Identification of a miRNA signature as a diagnostic and prognostic marker in renal cell carcinoma." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2021. http://dx.doi.org/10.29117/quarfe.2021.0109.
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Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). If diagnosed in later stages, ccRCC is associated with high renal cancer related morbidity and poor prognosis. Recently, microRNAs (miRNAs) have attracted interest as potential diagnostic and prognostic biomarkers due to their important role in cancer development and progression. Availability of big omics data in the cancer genome atlas (TCGA) coupled with data mining and machine learning have revolutionized the identification of robust diagnostic and prognostic signatures in different types of cancers. In this study, we have utilized the miRNA sequencing data of 516 ccRCC patients from TCGA to identify a diagnostic and prognostic signature by using a combined approach of differential expression analysis, survival analysis and machine learning. Differential expression analysis identified 30 downregulated and 20 upregulated miRNAs in the primary tumor as compared to solid tissue normal samples. Out of these 50 differentially expressed miRNAs, higher expression of 7 and lower expression of 6 miRNAs were found to be significantly associated with poor survival when analyzed using the Kaplan-Maier survival method. Pathway enrichment analyses related to the differentially expressed miRNAs revealed that fatty acid biosynthesis was the most significantly enriched KEGG pathway while proteoglycans in cancer pathway was enriched by the highest number of survival-associated miRNAs target genes. Differential expression and association with poor survival was used as a prefilter for training a support vector machine model capable of classifying tumor samples from solid tissue normal samples with an accuracy and precision of 99.23% and 98.50%, respectively. We have identified here a nine-miRNA signature in ccRCC patients that is capable of segregating tumor from normal tissue samples with high accuracy and precision. The future validation of this classification model in in a clinical cohort will support translation of these findings into clinical practice for early detection and follow-up of ccRCC.
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Hui Liu, Dong Yue, Lin Zhang, and Yu-Fei Huang. "A SVM based approach for miRNA target prediction." In 2008 International Conference on Machine Learning and Cybernetics (ICMLC). IEEE, 2008. http://dx.doi.org/10.1109/icmlc.2008.4621103.
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Hui Liu, Dong Yue, Lin Zhang, Shou-Jiang Gao, and Yufei Huang. "A machine learning approach for miRNA target prediction." In 2008 IEEE International Workshop on Genomic Signal Processing and Statistics (GENSIPS). IEEE, 2008. http://dx.doi.org/10.1109/gensips.2008.4555655.
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Papamichail, Dimitris, and Georgios Papamichail. "Incorporating miRNA target sites in protein-coding RNA." In 2010 IEEE International Conference on Bioinformatics and Biomedicine Workshops (BIBMW). IEEE, 2010. http://dx.doi.org/10.1109/bibmw.2010.5703832.
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Jung, Daekyoung, Sehi L'Yi, Bohyoung Kim, and Jinwook Seo. "Interactive visual analysis of miRNA target prediction results." In 2017 IEEE International Conference on Big Data and Smart Computing (BigComp). IEEE, 2017. http://dx.doi.org/10.1109/bigcomp.2017.7881694.
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Beretta, Stefano, Lucia Morganti, Elena Corni, Andrea Ferraro, Daniele Cesini, Daniele D'Agostino, Luciano Milanesi, and Ivan Merelli. "Low-Power Architectures for miRNA-Target Genome Wide Analysis." In 2017 25th Euromicro International Conference on Parallel, Distributed and Network-based Processing (PDP). IEEE, 2017. http://dx.doi.org/10.1109/pdp.2017.88.
Full textReports on the topic "MiRNA target"
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Arazi, Tzahi, Vivian Irish, and Asaph Aharoni. Micro RNA Targeted Transcription Factors for Fruit Quality Improvement. United States Department of Agriculture, July 2008. http://dx.doi.org/10.32747/2008.7592651.bard.
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Fruits are unique to flowering plants and represent an important component of human and animal diets. Development and maturation of tomato fruit is a well-programmed process, and yet, only a limited number of factors involved in its regulation have been characterized. Micro-RNAs (miRNAs) are small, endogenous RNAs that regulate gene expression in animals and plants. Plant miRNAs have a vital role in the generation of plant forms through post-transcriptional regulation of the accumulation of developmental regulators, especially transcription factors. Recently, we and others have demonstrated that miRNAs and other type of small RNAs are expressed in tomato fruit, and target putative transcription factors during its development and maturation. The original objectives of the approved proposal were: 1. To identify fruit miRNA transcription factor target genes through a bioinformatic approach. 2. To identify fruit miRNA transcription factor target genes up-regulated in tomato Dicer-like 1 silenced fruit. 3. To establish the biological functions of selected transcription factors and examine their utility for improving fleshy fruit quality trait. This project was approved by BARD as a feasibility study to allow initial experiments to peruse objective 2 as described above in order to provide initial evidence that miRNAs do play a role in fruit development. The approach planned to achieve objective 2, namely to identify miRNA transcription factor targets was to clone and silence the expression of a tomato DCL1 homolog in different stages of fruit development and examine alterations to gene expression in such a fruit in order to identify pathways and target genes that are regulated by miRNA via DCL1. In parallel, we characterized two transcription factors that are regulated by miRNAs in the fruit. We report here on the cloning of tomato DCL1 homolog, characterization of its expression in fruit flesh and peel of wild type and ripening mutants and generation of transgenic plants that silence SlDCL1 specifically in the fruit. Our results suggest that the tomato homolog of DCL1, which is the major plant enzyme involved in miRNA biogenesis, is present in fruit flesh and peel and differentially expressed during various stages of fruit development. In addition, its expression is altered in ripening mutants. We also report on the cloning and expression analysis of Sl_SBP and Sl_ARF transcription factors, which serve as targets of miR157 and miR160, respectively. Our data suggest that Sl_SBP levels are highest during fruit ripening supporting a role for this gene in that process. On the other hand Sl_ARF is strongly expressed in green fruit up to breaker indicating a role for that gene at preripening stage which is consistent with preliminary in_situ analyses that suggest expression in ovules of immature green fruit. The results of this feasibility study together with our previous results that miRNAs are expressed in the fruit indeed provide initial evidence that these regulators and their targets play roles in fruit development and ripening. These genes are expected to provide novel means for genetic improvement of tomato fleshy fruit.
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Lers, Amnon, and Pamela J. Green. Analysis of Small RNAs Associated with Plant Senescence. United States Department of Agriculture, March 2013. http://dx.doi.org/10.32747/2013.7593393.bard.
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Senescence is an agriculturally significant process due to its negative impact to crop yield and postharvest quality. The genetic regulatory systems controlling senescence induction and progress respond to both developmental and environmental stress signals and involve numerous gene expression changes. Knowledge about the key molecular factors which control senescence is very limited. MicroRNAs (miRNAs) are a class of small RNAs which typically function by guiding cleavage of target messenger RNAs. They have been shown to play major roles in a variety of plant processes including development, responses to environmental stresses, and senescence. The long-term goal of this work is to elucidate roles of small RNAs associated with plant senescence. The hypothesis underlying this research is that miRNA-mediated regulation makes important contributions to the senescence process in plants. Specific, original research objectives included: 1) Profiling of small RNAs from senescing plants; 2) Data Analysis and public access via a user-friendly web interface; 3) Validation of senescence-associated miRNAs and target RNAs; 4) Development of transgenic plants for functional analysis of miRNAs in Arabidopsis. Major revisions made in the research compared to the original work plan included 1) Exclusion of the planned work with tomato as recommended by the BARD review panel; 2) Performing miRNA study also in senescing Arabidopsis siliques, in addition to senescing leaves. To identify senescenceregulation of miRNAs in Arabidopsis thaliana, eight small RNA libraries were constructed and sequenced at four different stages of development and senescence from both leaves and siliques, resulting in more than 200 million genome-matched sequences. Parallel Analysis of RNA Ends (PARE) libraries, which enable the large-scale examination of miRNA-guided cleavage products, were also constructed and sequenced, resulting in over 750 million genome-matched sequences. These massive datasets lead to the identification of new miRNAs, as well as new regulation of known miRNAs and their target genes during senescence, many of which have established roles in nutrient responsiveness and cell structural integrity. In keeping with remobilization of nutrients thought to occur during senescence, many miRNAs and targets had opposite expression pattern changes between leaf and silique tissues during the progression of senescence. Taken together, these findings highlight the integral role that miRNAs may play in the remobilization of resources and alteration of cellular structure that is known to occur in senescence. Experiments were initiated for functional analysis of specific senescence-associated miRNAs and respective target genes. Transgenic Arabidopsis plants were generated in which miR408, found in this study to be significantly induced in leaf senescence, was over-expressed either constitutively or under a senescence-specific promoter. These plants are currently being characterized for any altered phenotypes. In addition T-DNA knock out mutants for various target genes identified in this research are being analyzed. This work provides insights about specific miRNAs that contribute to leaf and silique senescence. The knowledge generated may suggest new strategies to monitor and alter the progression of senescence in crops for agricultural improvement.
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Sun, Lina, Yanan Han, Hua Wang, Huanyu Liu, Shan Liu, Hongbin Yang, Xiaoxia Ren, and Ying Fang. MicroRNAs as Potential Biomarkers for the Diagnosis of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, February 2022. http://dx.doi.org/10.37766/inplasy2022.2.0027.
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Review question / Objective: The purpose of this systematic review was to systematically review the clinical studies regarding miRNAs as diagnostic biomarkers for inflammatory bowel disease and assess the overall diagnostic accuracy of miRNAs. Condition being studied: The symptoms of inflammatory bowel disease (IBD) are highly variable. The diagnosis of IBD must be made through medical history, physical, laboratory, radiologic, endoscopic, and histological examinations. However, these diagnostic techniques are not specific and sometimes even equivocal. Therefore, reliable biomarkers are urgently needed in the diagnosis of IBD. Several clinical and preclinical researches have shown that dysregulated microRNAs (miRNAs) play a crucial role in IBD development. miRNAs, as single-stranded noncoding RNAs that contain 22-24 nucleotides, can post-transcriptionally regulate gene expression by blocking mRNA translation or degrading target mRNAs. miRNAs are widely involved in physiological and pathological cellular processes, such as differentiation, proliferation and apoptosis. Besides, they are stable, noninvasive, and resistant to degradation by ribonucleases, making them valuable targets in the diagnosis, monitoring, prognosis, and treatment of diseases. To date, inconsistent results have been found about miRNA expression profiling in the patients with IBD. Moreover, the diagnostic accuracy of miRNAs for IBD has not been reported in any meta-analysis.
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Whitham, Steven A., Amit Gal-On, and Victor Gaba. Post-transcriptional Regulation of Host Genes Involved with Symptom Expression in Potyviral Infections. United States Department of Agriculture, June 2012. http://dx.doi.org/10.32747/2012.7593391.bard.
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Understanding how RNA viruses cause disease symptoms in their hosts is expected to provide information that can be exploited to enhance modern agriculture. The helper component-proteinase (HC-Pro) protein of potyviruses has been implicated in symptom development. Previously, we demonstrated that symptom expression is associated with binding of duplex small-interfering-RNA (duplex-siRNA) to a highly conserved FRNK amino acid motif in the HC-Pro of Zucchini yellow mosaic virus (ZYMV). This binding activity also alters host microRNA (miRNA) profiles. In Turnip mosaic virus (TuMV), which infects the model plant Arabidopsis, mutation of the FRNK motif to FINK was lethal providing further indication of the importance of this motif to HC-Pro function. In this continuation project, our goal was to further investigate how ZYMV and TuMV cause the mis-expression of genes in cucurbits and Arabidopsis, respectively, and to correlate altered gene expression with disease symptoms. Objective 1 was to examine the roles of aromatic and positively charged residues F164RNH and K215RLF adjacent to FR180NK in small RNA binding. Objective 2 was to determine the target genes of the miRNAs which change during HC-Pro expression in infected tissues and transgenic cucumber. Objective 3 was to characterize RNA silencing mechanisms underlying differential expression of host genes. Objective 4 was to analyze the function of miRNA target genes and differentially expressed genes in potyvirus-infected tissues. We found that the charged K/R amino acid residues in the FKNH and KRLF motifs are essential for virus viability. Replacement of K to I in FKNH disrupted duplex-siRNA binding and virus infectivity, while in KRLF mutants duplex-siRNA binding was maintained and virus infectivity was limited: symptomless following a recovery phenomenon. These findings expanded the duplex-siRNA binding activity of HC-Pro to include the adjacent FRNK and FRNH sites. ZYMV causes many squash miRNAs to hyper-accumulate such as miR166, miR390, mir168, and many others. Screening of mir target genes showed that only INCURVATA-4 and PHAVOLUTA were significantly upregulated following ZYMVFRNK infection. Supporting this finding, we found similar developmental symptoms in transgenic Arabidopsis overexpressing P1-HC-Pro of a range of potyviruses to those observed in miR166 mutants. We characterized increased transcription of AGO1 in response to infection with both ZYMV strains. Differences in viral siRNA profiles and accumulation between mild and severe virus infections were characterized by Illumina sequencing, probably due to the differences in HC-Pro binding activity. We determined that the TuMV FINK mutant could accumulate and cause symptoms in dcl2 dcl4 or dcl2 dcl3 dcl4 mutants similar to TuMV FRNK in wild type Arabidopsis plants. These dcl mutant plants are defective in antiviral defenses, and the results show that factors other than HC-ProFRNK motif can induce symptoms in virus-infected plants. As a result of this work, we have a better understanding of the FRNK and FKNH amino acid motifs of HC-Pro and their contributions to the duplex-siRNA binding functions. We have identified plant genes that potentially contribute to infectivity and symptoms of virus infected plants when they are mis-expressed during potyviral infections. The results establish that there are multiple underlying molecular mechanisms that lead viral pathogenicity, some dependent on HC-Pro. The potential benefits include the development of novel strategies for controlling diseases caused by viruses, methods to ensure stable expression of transgenes in genetically improved crops, and improved potyvirus vectors for expression of proteins or peptides in plants.
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Green, Pamela J. Genome-Wide Analysis of miRNA targets in Brachypodium and Biomass Energy Crops. Office of Scientific and Technical Information (OSTI), August 2015. http://dx.doi.org/10.2172/1209217.
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Grumet, Rebecca, Rafael Perl-Treves, and Jack Staub. Ethylene Mediated Regulation of Cucumis Reproduction - from Sex Expression to Fruit Set. United States Department of Agriculture, February 2010. http://dx.doi.org/10.32747/2010.7696533.bard.
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Reproductive development is a critical determinant of agricultural yield. For species with unisexual flowers, floral secualdifferentation adds additional complexity, that can influenec productivity. The hormone ethylene has long, been known to play a primary role in sex determination in the Cucumis species cucumber (C. sativus) and melon (C. melo). Our objectives were to: (1) Determine critical sites of ethylene production and perception for sex determination; (2) Identify additional ethylene related genes associated with sex expression; and (3) Examine the role of environment ami prior fruit set on sex expression, pistillate flower maturation, and fruit set. We made progress in each of these areas. (1) Transgenic melon produced with the Arabidopsis dominant negative ethylene perception mutant gene, etrl-1, under the control of floral primordia targeted promoters [AP3 (petal and stamen) and CRC (carpel and nectary)], showed that ethylene perception by the stamen primordia, rather than carpel primordia, is critical for carpel development at the time of sex determination. Transgenic melons also were produced with the ethylene production enzyme gene. ACS, encoding l-aminocyclopropane-lcarboylate synthase, fused to the AP3 or CRC promoters. Consistent with the etr1-1 results, CRC::ACS did not increase femaleness; however, AP3::ACS reduced or eliminated male flower production. The effects of AP3:ACS were stronger than those of 35S::ACS plants, demonstratin g the importance of targeted expression, while avoiding disadvantages of constitutive ethylene production. (2) Linkage analysis coupled with SNP discovery was per formed on ethylene and floral development genes in cucumber populations segregating for the three major sex genes. A break-through towards cloning the cucumber M gene occurred when the melon andromonoecious gene (a), an ACS gene, was cloned in 2008. Both cucumber M and melon a suppress stamen development in pistillate flowers. We hypothesized that cucumber M could be orthologous to melon a, and found that mutations in CsACS2 co-segregated perfectly with the M gene. We also sought to identify miRNA molecules associated with sex determination. miRNA159, whose target in Arabidopsis is GAMYB[a transcription factor gene mediating response to10 gibberellin (GA)], was more highly expressed in young female buds than male. Since GA promotes maleness in cucumber, a micro RNA that counteracts GAMYB could promote femaleness. miRNA157, which in other plants targets transcription factors involved in flower development , was expressed in young male buds and mature flower anthers. (3) Gene expression profiling showed that ethylene-, senescence-, stress- and ubiquitin-related genes were up-regulated in senescing and inhibited fruits, while those undergoing successful fruit set up-regulated photosynthesis, respiration and metabolic genes. Melon plants can change sex expression in response to environmental conditions, leading to changes in yield potential. Unique melon lines with varying sex expression were developed and evaluated in the field in Hancock, Wisconsin . Environmental changes during the growing season influenced sex expression in highly inbred melon lines. Collectively these results are of significance for understanding regulation of sex expression. The fact that both cucumber sex loci identified so far (F and M) encode isoforms of the same ethylene synthesis enzyme, underscores the importance of ethylene as the main sex determining hormone in cucumber. The targeting studies give insight into developmental switch points and suggest a means to develop lines with earlier carpel-bearing flower production and fruit set. These results are of significance for understanding regulation of sex expression to facilitate shorter growing seasons and earlier time to market. Field results provide information for development of management strategies for commercial production of melon cultivars with different sex expression characteristics during fruit production.
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Whitham, Steven A., Amit Gal-On, and Tzahi Arazi. Functional analysis of virus and host components that mediate potyvirus-induced diseases. United States Department of Agriculture, March 2008. http://dx.doi.org/10.32747/2008.7591732.bard.
Full textAbstract:
The mechanisms underlying the development of symptoms in response to virus infection remain to be discovered in plants. Insight into symptoms induced by potyviruses comes from evidence implicating the potyviral HC-Pro protein in symptom development. In particular, recent studies link the development of symptoms in infected plants to HC-Pro's ability to interfere with small RNA metabolism and function in plant hosts. Moreover, mutation of the highly conserved FRNK amino acid motif to FINK in the HC-Pro of Zucchini yellow mosaic virus (ZYMV) converts a severe strain into an asymptomatic strain, but does not affect virus accumulation in cucurbit hosts. The ability of this FINK mutation to uncouple symptoms from virus accumulation creates a unique opportunity to study symptom etiology, which is usually confounded by simultaneous attenuation of both symptoms and virus accumulation. Our goal was to determine how mutations in the conserved FRNK motif affect host responses to potyvirus infection in cucurbits and Arabidopsis thaliana. Our first objective was to define those amino acids in the FRNK motif that are required for symptoms by mutating the FRNK motif in ZYMV and Turnip mosaic virus (TuMV). Symptom expression and accumulation of resulting mutant viruses in cucurbits and Arabidopsis was determined. Our second objective was to identify plant genes associated with virus disease symptoms by profiling gene expression in cucurbits and Arabidopsis in response to mutant and wild type ZYMV and TuMV, respectively. Genes from the two host species that are differentially expressed led us to focus on a subset of genes that are expected to be involved in symptom expression. Our third objective was to determine the functions of small RNA species in response to mutant and wild type HC-Pro protein expression by monitoring the accumulation of small RNAs and their targets in Arabidopsis and cucurbit plants infected with wild type and mutant TuMV and ZYMV, respectively. We have found that the maintenance of the charge of the amino acids in the FRNK motif of HC-Pro is required for symptom expression. Reduced charge (FRNA, FRNL) lessen virus symptoms, and maintain the suppression of RNA silencing. The FRNK motif is involved in binding of small RNA species including microRNAs (miRNA) and short interfering RNAs (siRNA). This binding activity mediated by the FRNK motif has a role in protecting the viral genome from degradation by the host RNA silencing system. However, it also provides a mechanism by which the FRNK motif participates in inducing the symptoms of viral infection. Small RNA species, such as miRNA and siRNA, can regulate the functions of plant genes that affect plant growth and development. Thus, this binding activity suggests a mechanism by which ZYMVHC-Pro can interfere with plant development resulting in disease symptoms. Because the host genes regulated by small RNAs are known, we have identified candidate host genes that are expected to play a role in symptoms when their regulation is disrupted during viral infections. As a result of this work, we have a better understanding of the FRNK amino acid motif of HC-Pro and its contribution to the functions of HC-Pro, and we have identified plant genes that potentially contribute to symptoms of virus infected plants when their expression becomes misregulated during potyviral infections. The results set the stage to establish the roles of specific host genes in viral pathogenicity. The potential benefits include the development of novel strategies for controlling diseases caused by viruses, methods to ensure stable expression of transgenes in genetically improved crops, and improved potyvirus vectors for expression of proteins or peptides in plants.