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Journal articles on the topic 'RNA G-Quadruplexes'

Author: Grafiati

Published: 30 November 2024

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1

Agarwal, Tani, Gopal Jayaraj, Satya Prakash Pandey, Prachi Agarwala, and Souvik Maiti. "RNA G-Quadruplexes: G-quadruplexes with “U” Turns." Current Pharmaceutical Design 18, no. 14 (March 1, 2012): 2102–11. http://dx.doi.org/10.2174/138161212799958468.

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2

Zhang, Rongxin, Yajun Liu, Xingxing Zhang, Ke Xiao, Yue Hou, Hongde Liu, and Xiao Sun. "Detecting and Profiling Endogenous RNA G-Quadruplexes in the Human Transcriptome." International Journal of Molecular Sciences 22, no. 15 (July 27, 2021): 8012. http://dx.doi.org/10.3390/ijms22158012.

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G-quadruplexes are the non-canonical nucleic acid structures that are preferentially formed in G-rich regions. This structure has been shown to be associated with many biological functions. Regardless of the broad efforts on DNA G-quadruplexes, we still have limited knowledge on RNA G-quadruplexes, especially in a transcriptome-wide manner. Herein, by integrating the DMS-seq and the bioinformatics pipeline, we profiled and depicted the RNA G-quadruplexes in the human transcriptome. The genes that contain RNA G-quadruplexes in their specific regions are significantly related to immune pathways and the COVID-19-related gene sets. Bioinformatics analysis reveals the potential regulatory functions of G-quadruplexes on miRNA targeting at the scale of the whole transcriptome. In addition, the G-quadruplexes are depleted in the putative, not the real, PAS-strong poly(A) sites, which may weaken the possibility of such sites being the real cleaved sites. In brief, our study provides insight into the potential function of RNA G-quadruplexes in post-transcription.

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3

Millevoi, Stefania, Hervé Moine, and Stéphan Vagner. "G-quadruplexes in RNA biology." Wiley Interdisciplinary Reviews: RNA 3, no. 4 (April 4, 2012): 495–507. http://dx.doi.org/10.1002/wrna.1113.

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4

Li, Wei, Weiwu Zeng, Yi Chen, Fang Wang, Fan Wu, Xiaocheng Weng, and Xiang Zhou. "Biotinylation and isolation of an RNA G-quadruplex based on its peroxidase-mimicking activity." Analyst 144, no. 15 (2019): 4472–76. http://dx.doi.org/10.1039/c9an00353c.

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5

Mestre-Fos, Santi, Petar I. Penev, Suttipong Suttapitugsakul, Michael Hu, Chieri Ito, Anton S. Petrov, Roger M. Wartell, Ronghu Wu, and Loren Dean Williams. "G-Quadruplexes in Human Ribosomal RNA." Journal of Molecular Biology 431, no. 10 (May 2019): 1940–55. http://dx.doi.org/10.1016/j.jmb.2019.03.010.

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6

Koralewska, Natalia, Agnieszka Szczepanska, Kinga Ciechanowska, Marta Wojnicka, Maria Pokornowska, Marek C. Milewski, Dorota Gudanis, et al. "RNA and DNA G-quadruplexes bind to human dicer and inhibit its activity." Cellular and Molecular Life Sciences 78, no. 7 (March 17, 2021): 3709–24. http://dx.doi.org/10.1007/s00018-021-03795-w.

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AbstractGuanine (G)-rich single-stranded nucleic acids can adopt G-quadruplex structures. Accumulating evidence indicates that G-quadruplexes serve important regulatory roles in fundamental biological processes such as DNA replication, transcription, and translation, while aberrant G-quadruplex formation is linked to genome instability and cancer. Understanding the biological functions played by G-quadruplexes requires detailed knowledge of their protein interactome. Here, we report that both RNA and DNA G-quadruplexes are bound by human Dicer in vitro. Using in vitro binding assays, mutation studies, and computational modeling we demonstrate that G-quadruplexes can interact with the Platform–PAZ–Connector helix cassette of Dicer, the region responsible for anchoring microRNA precursors (pre-miRNAs). Consequently, we show that G-quadruplexes efficiently and stably inhibit the cleavage of pre-miRNA by Dicer. Our data highlight the potential of human Dicer for binding of G-quadruplexes and allow us to propose a G-quadruplex-driven sequestration mechanism of Dicer regulation.

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7

Rouleau, Samuel, Jean-Pierre Sehi Glouzon, Andrea Brumwell, Martin Bisaillon, and Jean-Pierre Perreault. "3′ UTR G-quadruplexes regulate miRNA binding." RNA 23, no. 8 (May 4, 2017): 1172–79. http://dx.doi.org/10.1261/rna.060962.117.

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8

Criscuolo, Andrea, Ettore Napolitano, Claudia Riccardi, Domenica Musumeci, Chiara Platella, and Daniela Montesarchio. "Insights into the Small Molecule Targeting of Biologically Relevant G-Quadruplexes: An Overview of NMR and Crystal Structures." Pharmaceutics 14, no. 11 (November 1, 2022): 2361. http://dx.doi.org/10.3390/pharmaceutics14112361.

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G-quadruplexes turned out to be important targets for the development of novel targeted anticancer/antiviral therapies. More than 3000 G-quadruplex small-molecule ligands have been described, with most of them exerting anticancer/antiviral activity by inducing telomeric damage and/or altering oncogene or viral gene expression in cancer cells and viruses, respectively. For some ligands, in-depth NMR and/or crystallographic studies were performed, providing detailed knowledge on their interactions with diverse G-quadruplex targets. Here, the PDB-deposited NMR and crystal structures of the complexes between telomeric, oncogenic or viral G-quadruplexes and small-molecule ligands, of both organic and metal-organic nature, have been summarized and described based on the G-quadruplex target, from telomeric DNA and RNA G-quadruplexes to DNA oncogenic G-quadruplexes, and finally to RNA viral G-quadruplexes. An overview of the structural details of these complexes is here provided to guide the design of novel ligands targeting more efficiently and selectively cancer- and virus-related G-quadruplex structures.

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9

Teng, Ye, Hisae Tateishi-Karimata, and Naoki Sugimoto. "RNA G-Quadruplexes Facilitate RNA Accumulation in G-Rich Repeat Expansions." Biochemistry 59, no. 21 (April 17, 2020): 1972–80. http://dx.doi.org/10.1021/acs.biochem.0c00130.

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10

Dumetz, Franck, Eugene Yui-Ching Chow, Lynne M. Harris, Shiau Wei Liew, Anders Jensen, Mubarak I. Umar, Betty Chung, Ting Fung Chan, Catherine J. Merrick, and Chun Kit Kwok. "G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum." Nucleic Acids Research 49, no. 21 (November 18, 2021): 12486–501. http://dx.doi.org/10.1093/nar/gkab1095.

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Abstract G-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasite Plasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form in P. falciparum RNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standard in silico algorithms. However, in vitro biophysical assays verified formation of non-canonical motifs. The G-quadruplexes in the P. falciparum transcriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encode PfEMP1 virulence factors, stress response genes and DNA binding proteins. In vitro translation experiments and in vivo measures of translation efficiency showed that G-quadruplexes can influence the translation of P. falciparum mRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.

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11

Sanchez-Martin, Victoria, Miguel Soriano, and Jose Antonio Garcia-Salcedo. "Quadruplex Ligands in Cancer Therapy." Cancers 13, no. 13 (June 24, 2021): 3156. http://dx.doi.org/10.3390/cancers13133156.

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Nucleic acids can adopt alternative secondary conformations including four-stranded structures known as quadruplexes. To date, quadruplexes have been demonstrated to exist both in human chromatin DNA and RNA. In particular, quadruplexes are found in guanine-rich sequences constituting G-quadruplexes, and in cytosine-rich sequences forming i-Motifs as a counterpart. Quadruplexes are associated with key biological processes ranging from transcription and translation of several oncogenes and tumor suppressors to telomeres maintenance and genome instability. In this context, quadruplexes have prompted investigations on their possible role in cancer biology and the evaluation of small-molecule ligands as potential therapeutic agents. This review aims to provide an updated close-up view of the literature on quadruplex ligands in cancer therapy, by grouping together ligands for DNA and RNA G-quadruplexes and DNA i-Motifs.

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12

Illodo, Sara, Cibrán Pérez-González, Ramiro Barcia, Flor Rodríguez-Prieto, Wajih Al-Soufi, and Mercedes Novo. "Spectroscopic Characterization of Mitochondrial G-Quadruplexes." International Journal of Molecular Sciences 23, no. 2 (January 15, 2022): 925. http://dx.doi.org/10.3390/ijms23020925.

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Guanine quadruplexes (G4s) are highly polymorphic four-stranded structures formed within guanine-rich DNA and RNA sequences that play a crucial role in biological processes. The recent discovery of the first G4 structures within mitochondrial DNA has led to a small revolution in the field. In particular, the G-rich conserved sequence block II (CSB II) can form different types of G4s that are thought to play a crucial role in replication. In this study, we decipher the most relevant G4 structures that can be formed within CSB II: RNA G4 at the RNA transcript, DNA G4 within the non-transcribed strand and DNA:RNA hybrid between the RNA transcript and the non-transcribed strand. We show that the more abundant, but unexplored, G6AG7 (37%) and G6AG8 (35%) sequences in CSB II yield more stable G4s than the less profuse G5AG7 sequence. Moreover, the existence of a guanine located 1 bp upstream promotes G4 formation. In all cases, parallel G4s are formed, but their topology changes from a less ordered to a highly ordered G4 when adding small amounts of potassium or sodium cations. Circular dichroism was used due to discriminate different conformations and topologies of nucleic acids and was complemented with gel electrophoresis and fluorescence spectroscopy studies.

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13

Beaudoin, Jean-Denis, Rachel Jodoin, and Jean-Pierre Perreault. "In-line probing of RNA G-quadruplexes." Methods 64, no. 1 (November 2013): 79–87. http://dx.doi.org/10.1016/j.ymeth.2013.02.017.

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14

Reina, Chiara, and Vincenzo Cavalieri. "Epigenetic Modulation of Chromatin States and Gene Expression by G-Quadruplex Structures." International Journal of Molecular Sciences 21, no. 11 (June 11, 2020): 4172. http://dx.doi.org/10.3390/ijms21114172.

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G-quadruplexes are four-stranded helical nucleic acid structures formed by guanine-rich sequences. A considerable number of studies have revealed that these noncanonical structural motifs are widespread throughout the genome and transcriptome of numerous organisms, including humans. In particular, G-quadruplexes occupy strategic locations in genomic DNA and both coding and noncoding RNA molecules, being involved in many essential cellular and organismal functions. In this review, we first outline the fundamental structural features of G-quadruplexes and then focus on the concept that these DNA and RNA structures convey a distinctive layer of epigenetic information that is critical for the complex regulation, either positive or negative, of biological activities in different contexts. In this framework, we summarize and discuss the proposed mechanisms underlying the functions of G-quadruplexes and their interacting factors. Furthermore, we give special emphasis to the interplay between G-quadruplex formation/disruption and other epigenetic marks, including biochemical modifications of DNA bases and histones, nucleosome positioning, and three-dimensional organization of chromatin. Finally, epigenetic roles of RNA G-quadruplexes in post-transcriptional regulation of gene expression are also discussed. Undoubtedly, the issues addressed in this review take on particular importance in the field of comparative epigenetics, as well as in translational research.

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15

Sanchez-Martin, Victoria, Carmen Lopez-Pujante, Miguel Soriano-Rodriguez, and Jose A. Garcia-Salcedo. "An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer." International Journal of Molecular Sciences 21, no. 23 (November 24, 2020): 8900. http://dx.doi.org/10.3390/ijms21238900.

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Non-canonical, four-stranded nucleic acids secondary structures are present within regulatory regions in the human genome and transcriptome. To date, these quadruplex structures include both DNA and RNA G-quadruplexes, formed in guanine-rich sequences, and i-Motifs, found in cytosine-rich sequences, as their counterparts. Quadruplexes have been extensively associated with cancer, playing an important role in telomere maintenance and control of genetic expression of several oncogenes and tumor suppressors. Therefore, quadruplex structures are considered attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this review, we provide a general overview about recent research on the implications of quadruplex structures in cancer, firstly gathering together DNA G-quadruplexes, RNA G-quadruplexes as well as DNA i-Motifs.

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16

Tassinari, Martina, Sara N. Richter, and Paolo Gandellini. "Biological relevance and therapeutic potential of G-quadruplex structures in the human noncoding transcriptome." Nucleic Acids Research 49, no. 7 (March 15, 2021): 3617–33. http://dx.doi.org/10.1093/nar/gkab127.

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Abstract Noncoding RNAs are functional transcripts that are not translated into proteins. They represent the largest portion of the human transcriptome and have been shown to regulate gene expression networks in both physiological and pathological cell conditions. Research in this field has made remarkable progress in the comprehension of how aberrations in noncoding RNA drive relevant disease-associated phenotypes; however, the biological role and mechanism of action of several noncoding RNAs still need full understanding. Besides fulfilling its function through sequence-based mechanisms, RNA can form complex secondary and tertiary structures which allow non-canonical interactions with proteins and/or other nucleic acids. In this context, the presence of G-quadruplexes in microRNAs and long noncoding RNAs is increasingly being reported. This evidence suggests a role for RNA G-quadruplexes in controlling microRNA biogenesis and mediating noncoding RNA interaction with biological partners, thus ultimately regulating gene expression. Here, we review the state of the art of G-quadruplexes in the noncoding transcriptome, with their structural and functional characterization. In light of the existence and further possible development of G-quadruplex binders that modulate G-quadruplex conformation and protein interactions, we also discuss the therapeutic potential of G-quadruplexes as targets to interfere with disease-associated noncoding RNAs.

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17

Roxo, Carolina, and Anna Pasternak. "Changes in physicochemical and anticancer properties modulated by chemically modified sugar moieties within sequence-related G-quadruplex structures." PLOS ONE 17, no. 8 (August 23, 2022): e0273528. http://dx.doi.org/10.1371/journal.pone.0273528.

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We systematically investigated the influence of locked nucleic acid (LNA), unlock nucleic acid (UNA), and 2’-O-methyl-RNA (2’-O-Me-RNA) residues on the thermal stability, structure folding topology, biological activity and enzymatic resistance of three sequence-related DNA G-quadruplexes. In order to better understand the mechanism of action of the studied modifications, a single-position substitution in the loops or G-tetrads was performed and their influence was analyzed for a total of twenty-seven modified G-quadruplex variants. The studies show that the influence of each modification on the physicochemical properties of G-quadruplexes is position-dependent, due to mutual interactions between G-tetrads, loops, and additional guanosine at 5’ or 3’ end. Nevertheless, the anticancer activity of the modified G-quadruplexes is determined by their structure, thus also by the local changes of chemical character of sugar moieties, what might influence the specific interactions with therapeutic targets. In general, UNA modifications are efficient modulators of the G-quadruplex thermodynamic stability, however they are poor tools to improve the anticancer properties. In contrast, LNA and 2’-O-Me-RNA modified G-quadruplexes demonstrated certain antiproliferative potential and might be used as molecular tools for designing novel G-quadruplex-based therapeutics.

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18

Xu, Yan, and Makoto Komiyama. "G-Quadruplexes in Human Telomere: Structures, Properties, and Applications." Molecules 29, no. 1 (December 27, 2023): 174. http://dx.doi.org/10.3390/molecules29010174.

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G-quadruplexes, intricate four-stranded structures composed of G-tetrads formed by four guanine bases, are prevalent in both DNA and RNA. Notably, these structures play pivotal roles in human telomeres, contributing to essential cellular functions. Additionally, the existence of DNA:RNA hybrid G-quadruplexes adds a layer of complexity to their structural diversity. This review provides a comprehensive overview of recent advancements in unraveling the intricacies of DNA and RNA G-quadruplexes within human telomeres. Detailed insights into their structural features are presented, encompassing the latest developments in chemical approaches designed to probe these G-quadruplex structures. Furthermore, this review explores the applications of G-quadruplex structures in targeting human telomeres. Finally, the manuscript outlines the imminent challenges in this evolving field, setting the stage for future investigations.

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19

Liu, Xiao, and Yan Xu. "HnRNPA1 Specifically Recognizes the Base of Nucleotide at the Loop of RNA G-Quadruplex." Molecules 23, no. 1 (January 22, 2018): 237. http://dx.doi.org/10.3390/molecules23010237.

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Human telomere RNA performs various cellular functions, such as telomere length regulation, heterochromatin formation, and end protection. We recently demonstrated that the loops in the RNA G-quadruplex are important in the interaction of telomere RNA with heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Here, we report on a detailed analysis of hnRNPA1 binding to telomere RNA G-quadruplexes with a group of loop variants using an electrophoretic mobility shift assay (EMSA) and circular dichroism (CD) spectroscopy. We found that the hnRNPA1 binds to RNA G-quadruplexes with the 2’-O-methyl and DNA loops, but fails to bind with the abasic RNA and DNA loops. These results suggested that hnRNPA1 binds to the loop of the RNA G-quadruplex by recognizing the base of the loop’s nucleotides. The observation provides the first evidence that the base of the loop’s nucleotides is a key factor for hnRNPA1 specifically recognizing the RNA G-quadruplex.

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20

Lyu, Kaixin, Eugene Yui-Ching Chow, Xi Mou, Ting-Fung Chan, and Chun Kit Kwok. "RNA G-quadruplexes (rG4s): genomics and biological functions." Nucleic Acids Research 49, no. 10 (March 27, 2021): 5426–50. http://dx.doi.org/10.1093/nar/gkab187.

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Abstract G-quadruplexes (G4s) are non-classical DNA or RNA secondary structures that have been first observed decades ago. Over the years, these four-stranded structural motifs have been demonstrated to have significant regulatory roles in diverse biological processes, but challenges remain in detecting them globally and reliably. Compared to DNA G4s (dG4s), the study of RNA G4s (rG4s) has received less attention until recently. In this review, we will summarize the innovative high-throughput methods recently developed to detect rG4s on a transcriptome-wide scale, highlight the many novel and important functions of rG4 being discovered in vivo across the tree of life, and discuss the key biological questions to be addressed in the near future.

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21

Kwok, Chun Kit, Giovanni Marsico, and Shankar Balasubramanian. "Detecting RNA G-Quadruplexes (rG4s) in the Transcriptome." Cold Spring Harbor Perspectives in Biology 10, no. 7 (July 2018): a032284. http://dx.doi.org/10.1101/cshperspect.a032284.

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22

Brázda, Václav, Yu Luo, Martin Bartas, Patrik Kaura, Otilia Porubiaková, Jiří Šťastný, Petr Pečinka, et al. "G-Quadruplexes in the Archaea Domain." Biomolecules 10, no. 9 (September 21, 2020): 1349. http://dx.doi.org/10.3390/biom10091349.

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The importance of unusual DNA structures in the regulation of basic cellular processes is an emerging field of research. Amongst local non-B DNA structures, G-quadruplexes (G4s) have gained in popularity during the last decade, and their presence and functional relevance at the DNA and RNA level has been demonstrated in a number of viral, bacterial, and eukaryotic genomes, including humans. Here, we performed the first systematic search of G4-forming sequences in all archaeal genomes available in the NCBI database. In this article, we investigate the presence and locations of G-quadruplex forming sequences using the G4Hunter algorithm. G-quadruplex-prone sequences were identified in all archaeal species, with highly significant differences in frequency, from 0.037 to 15.31 potential quadruplex sequences per kb. While G4 forming sequences were extremely abundant in Hadesarchaea archeon (strikingly, more than 50% of the Hadesarchaea archaeon isolate WYZ-LMO6 genome is a potential part of a G4-motif), they were very rare in the Parvarchaeota phylum. The presence of G-quadruplex forming sequences does not follow a random distribution with an over-representation in non-coding RNA, suggesting possible roles for ncRNA regulation. These data illustrate the unique and non-random localization of G-quadruplexes in Archaea.

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23

Jayaraj, Gopal Gunanathan, Satyaprakash Pandey, Vinod Scaria, and Souvik Maiti. "Potential G-quadruplexes in the human long non-coding transcriptome." RNA Biology 9, no. 1 (January 2012): 81–89. http://dx.doi.org/10.4161/rna.9.1.18047.

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24

Puig Lombardi, Emilia, and Arturo Londoño-Vallejo. "A guide to computational methods for G-quadruplex prediction." Nucleic Acids Research 48, no. 1 (November 22, 2019): 1–15. http://dx.doi.org/10.1093/nar/gkz1097.

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Abstract Guanine-rich nucleic acids can fold into the non-B DNA or RNA structures called G-quadruplexes (G4). Recent methodological developments have allowed the characterization of specific G-quadruplex structures in vitro as well as in vivo, and at a much higher throughput, in silico, which has greatly expanded our understanding of G4-associated functions. Typically, the consensus motif G3+N1–7G3+N1–7G3+N1–7G3+ has been used to identify potential G-quadruplexes from primary sequence. Since, various algorithms have been developed to predict the potential formation of quadruplexes directly from DNA or RNA sequences and the number of studies reporting genome-wide G4 exploration across species has rapidly increased. More recently, new methodologies have also appeared, proposing other estimates which consider non-canonical sequences and/or structure propensity and stability. The present review aims at providing an updated overview of the current open-source G-quadruplex prediction algorithms and straightforward examples of their implementation.

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Asamitsu, Sefan, Masayuki Takeuchi, Susumu Ikenoshita, Yoshiki Imai, Hirohito Kashiwagi, and Norifumi Shioda. "Perspectives for Applying G-Quadruplex Structures in Neurobiology and Neuropharmacology." International Journal of Molecular Sciences 20, no. 12 (June 13, 2019): 2884. http://dx.doi.org/10.3390/ijms20122884.

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The most common form of DNA is a right-handed helix or the B-form DNA. DNA can also adopt a variety of alternative conformations, non-B-form DNA secondary structures, including the DNA G-quadruplex (DNA-G4). Furthermore, besides stem-loops that yield A-form double-stranded RNA, non-canonical RNA G-quadruplex (RNA-G4) secondary structures are also observed. Recent bioinformatics analysis of the whole-genome and transcriptome obtained using G-quadruplex–specific antibodies and ligands, revealed genomic positions of G-quadruplexes. In addition, accumulating evidence pointed to the existence of these structures under physiologically- and pathologically-relevant conditions, with functional roles in vivo. In this review, we focused on DNA-G4 and RNA-G4, which may have important roles in neuronal function, and reveal mechanisms underlying neurological disorders related to synaptic dysfunction. In addition, we mention the potential of G-quadruplexes as therapeutic targets for neurological diseases.

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Volná, Adriana, Martin Bartas, Václav Karlický, Jakub Nezval, Kristýna Kundrátová, Petr Pečinka, Vladimír Špunda, and Jiří Červeň. "G-Quadruplex in Gene Encoding Large Subunit of Plant RNA Polymerase II: A Billion-Year-Old Story." International Journal of Molecular Sciences 22, no. 14 (July 9, 2021): 7381. http://dx.doi.org/10.3390/ijms22147381.

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G-quadruplexes have long been perceived as rare and physiologically unimportant nucleic acid structures. However, several studies have revealed their importance in molecular processes, suggesting their possible role in replication and gene expression regulation. Pathways involving G-quadruplexes are intensively studied, especially in the context of human diseases, while their involvement in gene expression regulation in plants remains largely unexplored. Here, we conducted a bioinformatic study and performed a complex circular dichroism measurement to identify a stable G-quadruplex in the gene RPB1, coding for the RNA polymerase II large subunit. We found that this G-quadruplex-forming locus is highly evolutionarily conserved amongst plants sensu lato (Archaeplastida) that share a common ancestor more than one billion years old. Finally, we discussed a new hypothesis regarding G-quadruplexes interacting with UV light in plants to potentially form an additional layer of the regulatory network.

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27

Hagihara, Masaki. "Inhibition of protein synthesis through RNA-based tandem G-quadruplex formation." Chemical Communications 57, no. 65 (2021): 8063–66. http://dx.doi.org/10.1039/d1cc02995a.

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28

Bugaut, A., and S. Balasubramanian. "5'-UTR RNA G-quadruplexes: translation regulation and targeting." Nucleic Acids Research 40, no. 11 (February 20, 2012): 4727–41. http://dx.doi.org/10.1093/nar/gks068.

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29

Shrestha, Prakash, Shan Xiao, Soma Dhakal, Zheng Tan, and Hanbin Mao. "Nascent RNA transcripts facilitate the formation of G-quadruplexes." Nucleic Acids Research 42, no. 11 (May 14, 2014): 7236–46. http://dx.doi.org/10.1093/nar/gku416.

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Berlyoung, April S., and Bruce A. Armitage. "Assembly and Characterization of RNA/DNA Hetero-G-Quadruplexes." Biochemistry 59, no. 42 (October 13, 2020): 4072–80. http://dx.doi.org/10.1021/acs.biochem.0c00657.

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31

Fay, Marta M., Shawn M. Lyons, and Pavel Ivanov. "RNA G-Quadruplexes in Biology: Principles and Molecular Mechanisms." Journal of Molecular Biology 429, no. 14 (July 2017): 2127–47. http://dx.doi.org/10.1016/j.jmb.2017.05.017.

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32

Umar, Mubarak I., and Chun Kit Kwok. "Specific suppression of D-RNA G-quadruplex–protein interaction with an L-RNA aptamer." Nucleic Acids Research 48, no. 18 (September 25, 2020): 10125–41. http://dx.doi.org/10.1093/nar/gkaa759.

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Abstract G-quadruplexes (G4s) are nucleic acid structure motifs that are of significance in chemistry and biology. The function of G4s is often governed by their interaction with G4-binding proteins. Few categories of G4-specific tools have been developed to inhibit G4–protein interactions; however, until now there is no aptamer tool being developed to do so. Herein, we present a novel L-RNA aptamer that can generally bind to D-RNA G-quadruplex (rG4) structure, and interfere with rG4–protein interaction. Using hTERC rG4 as the target for in vitro selection, we report the shortest L-aptamer being developed so far, with only 25 nucleotides. Notably, this new aptamer, L-Apt.4-1c, adopts a stem–loop structure with the loop folding into an rG4 motif with two G-quartet, demonstrates preferential binding toward rG4s over non-G4s and DNA G-quadruplexes (dG4s), and suppresses hTERC rG4–nucleolin interactions. We also show that inhibition of rG4–protein interaction using L-RNA aptamer L-Apt.4-1c is comparable to or better than G4-specific ligands such as carboxypyridostatin and QUMA-1 respectively, highlighting that our approach and findings expand the current G4 toolbox, and open a new avenue for diverse applications.

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Pavlova, Iuliia, Mikhail Iudin, Anastasiya Surdina, Vjacheslav Severov, and Anna Varizhuk. "G-Quadruplexes in Nuclear Biomolecular Condensates." Genes 14, no. 5 (May 13, 2023): 1076. http://dx.doi.org/10.3390/genes14051076.

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G-quadruplexes (G4s) have long been implicated in the regulation of chromatin packaging and gene expression. These processes require or are accelerated by the separation of related proteins into liquid condensates on DNA/RNA matrices. While cytoplasmic G4s are acknowledged scaffolds of potentially pathogenic condensates, the possible contribution of G4s to phase transitions in the nucleus has only recently come to light. In this review, we summarize the growing evidence for the G4-dependent assembly of biomolecular condensates at telomeres and transcription initiation sites, as well as nucleoli, speckles, and paraspeckles. The limitations of the underlying assays and the remaining open questions are outlined. We also discuss the molecular basis for the apparent permissive role of G4s in the in vitro condensate assembly based on the interactome data. To highlight the prospects and risks of G4-targeting therapies with respect to the phase transitions, we also touch upon the reported effects of G4-stabilizing small molecules on nuclear biomolecular condensates.

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Teng, Ye, Ming Zhu, and Zhidong Qiu. "G-quadruplexes in Repeat Expansion Disorders." International Journal of Molecular Sciences 24, no. 3 (January 25, 2023): 2375. http://dx.doi.org/10.3390/ijms24032375.

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The repeat expansions are the main genetic cause of various neurodegeneration diseases. More than ten kinds of repeat sequences with different lengths, locations, and structures have been confirmed in the past two decades. G-rich repeat sequences, such as CGG and GGGGCC, are reported to form functional G-quadruplexes, participating in many important bioprocesses. In this review, we conducted an overview concerning the contribution of G-quadruplex in repeat expansion disorders and summarized related mechanisms in current pathological studies, including the increasing genetic instabilities in replication and transcription, the toxic RNA foci formed in neurons, and the loss/gain function of proteins and peptides. Furthermore, novel strategies targeting G-quadruplex repeats were developed based on the understanding of disease mechanism. Small molecules and proteins binding to G-quadruplex in repeat expansions were investigated to protect neurons from dysfunction and delay the progression of neurodegeneration. In addition, the effects of environment on the stability of G-quadruplex were discussed, which might be critical factors in the pathological study of repeat expansion disorders.

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Falabella, Micol, Rafael J. Fernandez, F. Brad Johnson, and Brett A. Kaufman. "Potential Roles for G-Quadruplexes in Mitochondria." Current Medicinal Chemistry 26, no. 16 (August 26, 2019): 2918–32. http://dx.doi.org/10.2174/0929867325666180228165527.

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Some DNA or RNA sequences rich in guanine (G) nucleotides can adopt noncanonical conformations known as G-quadruplexes (G4). In the nuclear genome, G4 motifs have been associated with genome instability and gene expression defects, but they are increasingly recognized to be regulatory structures. Recent studies have revealed that G4 structures can form in the mitochondrial genome (mtDNA) and potential G4 forming sequences are associated with the origin of mtDNA deletions. However, little is known about the regulatory role of G4 structures in mitochondria. In this short review, we will explore the potential for G4 structures to regulate mitochondrial function, based on evidence from the nucleus.

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He, Lei, Zhenyu Meng, Qianqian Guo, Xiangyang Wu, Marie-Paule Teulade-Fichou, Edwin Kok Lee Yeow, and Fangwei Shao. "Fluorogenic Pt complexes distinguish the quantity and folding behavior of RNA G-quadruplexes between live cancerous and healthy cells." Chemical Communications 56, no. 92 (2020): 14459–62. http://dx.doi.org/10.1039/d0cc05622g.

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Dell’Oca, Maria Chiara, Roberto Quadri, Giulia Maria Bernini, Luca Menin, Lavinia Grasso, Diego Rondelli, Ozge Yazici, et al. "Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles." International Journal of Molecular Sciences 25, no. 6 (March 9, 2024): 3162. http://dx.doi.org/10.3390/ijms25063162.

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G-quadruplexes or G4s are non-canonical secondary structures of nucleic acids characterized by guanines arranged in stacked tetraplex arrays. Decades of research into these peculiar assemblies of DNA and RNA, fueled by the development and optimization of a vast array of techniques and assays, has resulted in a large amount of information regarding their structure, stability, localization, and biological significance in native systems. A plethora of articles have reported the roles of G-quadruplexes in multiple pathways across several species, ranging from gene expression regulation to RNA biogenesis and trafficking, DNA replication, and genome maintenance. Crucially, a large amount of experimental evidence has highlighted the roles of G-quadruplexes in cancer biology and other pathologies, pointing at these structurally unique guanine assemblies as amenable drug targets. Given the rapid expansion of this field of research, this review aims at summarizing all the relevant aspects of G-quadruplex biology by combining and discussing results from seminal works as well as more recent and cutting-edge experimental evidence. Additionally, the most common methodologies used to study G4s are presented to aid the reader in critically interpreting and integrating experimental data.

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Heddi, Brahim, Vee Vee Cheong, Herry Martadinata, and Anh Tuân Phan. "Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex." Proceedings of the National Academy of Sciences 112, no. 31 (July 20, 2015): 9608–13. http://dx.doi.org/10.1073/pnas.1422605112.

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Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex–protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures.

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Ida, Jeunice, Soo Chan, Jörn Glökler, Yee Lim, Yee Choong, and Theam Lim. "G-Quadruplexes as An Alternative Recognition Element in Disease-Related Target Sensing." Molecules 24, no. 6 (March 19, 2019): 1079. http://dx.doi.org/10.3390/molecules24061079.

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G-quadruplexes are made up of guanine-rich RNA and DNA sequences capable of forming noncanonical nucleic acid secondary structures. The base-specific sterical configuration of G-quadruplexes allows the stacked G-tetrads to bind certain planar molecules like hemin (iron (III)-protoporphyrin IX) to regulate enzymatic-like functions such as peroxidase-mimicking activity, hence the use of the term DNAzyme/RNAzyme. This ability has been widely touted as a suitable substitute to conventional enzymatic reporter systems in diagnostics. This review will provide a brief overview of the G-quadruplex architecture as well as the many forms of reporter systems ranging from absorbance to luminescence readouts in various platforms. Furthermore, some challenges and improvements that have been introduced to improve the application of G-quadruplex in diagnostics will be highlighted. As the field of diagnostics has evolved to apply different detection systems, the need for alternative reporter systems such as G-quadruplexes is also paramount.

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Raguseo, Federica, Souroprobho Chowdhury, Aisling Minard, and Marco Di Antonio. "Chemical-biology approaches to probe DNA and RNA G-quadruplex structures in the genome." Chemical Communications 56, no. 9 (2020): 1317–24. http://dx.doi.org/10.1039/c9cc09107f.

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G-quadruplexes are nucleic-acids secondary structures that can be formed under physiological conditions. In this review, we critically present the most relevant chemical-biology methods to probe the biological functions of G-quadruplex structures.

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Tosoni, Elena, Ilaria Frasson, Matteo Scalabrin, Rosalba Perrone, Elena Butovskaya, Matteo Nadai, Giorgio Palù, Dan Fabris, and Sara N. Richter. "Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription." Nucleic Acids Research 43, no. 18 (October 10, 2015): 8884–97. http://dx.doi.org/10.1093/nar/gkv897.

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Abstract Folding of the LTR promoter into dynamic G-quadruplex conformations has been shown to suppress its transcriptional activity in HIV-1. Here we sought to identify the proteins that control the folding of this region of proviral genome by inducing/stabilizing G-quadruplex structures. The implementation of electrophorethic mobility shift assay and pull-down experiments coupled with mass spectrometric analysis revealed that the cellular protein nucleolin is able to specifically recognize G-quadruplex structures present in the LTR promoter. Nucleolin recognized with high affinity and specificity the majority, but not all the possible G-quadruplexes folded by this sequence. In addition, it displayed greater binding preference towards DNA than RNA G-quadruplexes, thus indicating two levels of selectivity based on the sequence and nature of the target. The interaction translated into stabilization of the LTR G-quadruplexes and increased promoter silencing activity; in contrast, disruption of nucleolin binding in cells by both siRNAs and a nucleolin binding aptamer greatly increased LTR promoter activity. These data indicate that nucleolin possesses a specific and regulated activity toward the HIV-1 LTR promoter, which is mediated by G-quadruplexes. These observations provide new essential insights into viral transcription and a possible low mutagenic target for antiretroviral therapy.

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Wolfe, Andrew L., Kamini Singh, Yi Zhong, Philipp Drewe, Vinagolu K. Rajasekhar, Viraj R. Sanghvi, Konstantinos J. Mavrakis, et al. "RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer." Nature 513, no. 7516 (July 27, 2014): 65–70. http://dx.doi.org/10.1038/nature13485.

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Lorenz, Ronny, Stephan H. Bernhart, Jing Qin, Christian Honer zu Siederdissen, Andrea Tanzer, Fabian Amman, Ivo L. Hofacker, and Peter F. Stadler. "2D Meets 4G: G-Quadruplexes in RNA Secondary Structure Prediction." IEEE/ACM Transactions on Computational Biology and Bioinformatics 10, no. 4 (July 2013): 832–44. http://dx.doi.org/10.1109/tcbb.2013.7.

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Song, Jingwen, Jean-Pierre Perreault, Ivan Topisirovic, and Stéphane Richard. "RNA G-quadruplexes and their potential regulatory roles in translation." Translation 4, no. 2 (July 2, 2016): e1244031. http://dx.doi.org/10.1080/21690731.2016.1244031.

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Hagen, Timo, Anna L. Malinowska, Helen L. Lightfoot, Martina Bigatti, and Jonathan Hall. "Site-Specific Fluorophore Labeling of Guanosines in RNA G-Quadruplexes." ACS Omega 4, no. 5 (May 14, 2019): 8472–79. http://dx.doi.org/10.1021/acsomega.9b00704.

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Varshney, Dhaval, Jochen Spiegel, Katherine Zyner, David Tannahill, and Shankar Balasubramanian. "The regulation and functions of DNA and RNA G-quadruplexes." Nature Reviews Molecular Cell Biology 21, no. 8 (April 20, 2020): 459–74. http://dx.doi.org/10.1038/s41580-020-0236-x.

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Yangyuoru, Philip M., Amy Y. Q. Zhang, Zhe Shi, Deepak Koirala, Shankar Balasubramanian, and Hanbin Mao. "Mechanochemical Properties of Individual Human Telomeric RNA (TERRA) G-Quadruplexes." ChemBioChem 14, no. 15 (August 26, 2013): 1931–35. http://dx.doi.org/10.1002/cbic.201300350.

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Jodoin, R., L. Bauer, J. M. Garant, A. Mahdi Laaref, F. Phaneuf, and J. P. Perreault. "The folding of 5'-UTR human G-quadruplexes possessing a long central loop." RNA 20, no. 7 (May 27, 2014): 1129–41. http://dx.doi.org/10.1261/rna.044578.114.

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Pandey, Satyaprakash, Prachi Agarwala, and Souvik Maiti. "Effect of Loops and G-Quartets on the Stability of RNA G-Quadruplexes." Journal of Physical Chemistry B 117, no. 23 (May 29, 2013): 6896–905. http://dx.doi.org/10.1021/jp401739m.

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Göç, Yavuz Burak, Jakub Poziemski, Weronika Smolińska, Dominik Suwała, Grzegorz Wieczorek, and Dorota Niedzialek. "Tracking Topological and Electronic Effects on the Folding and Stability of Guanine-Deficient RNA G-Quadruplexes, Engineered with a New Computational Tool for De Novo Quadruplex Folding." International Journal of Molecular Sciences 23, no. 19 (September 20, 2022): 10990. http://dx.doi.org/10.3390/ijms231910990.

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The initial aim of this work was to elucidate the mutual influence of different single-stranded segments (loops and caps) on the thermodynamic stability of RNA G-quadruplexes. To this end, we used a new NAB-GQ-builder software program, to construct dozens of two-tetrad G-quadruplex topologies, based on a designed library of sequences. Then, to probe the sequence–morphology–stability relationships of the designed topologies, we performed molecular dynamics simulations. Their results provide guidance for the design of G-quadruplexes with balanced structures, and in turn programmable physicochemical properties for applications as biomaterials. Moreover, by comparative examinations of the single-stranded segments of three oncogene promoter G-quadruplexes, we assess their druggability potential for future therapeutic strategies. Finally, on the basis of a thorough analysis at the quantum mechanical level of theory on a series of guanine assemblies, we demonstrate how a valence tautomerism, triggered by a coordination of cations, initiates the process of G-quadruplex folding, and we propose a sequential folding mechanism, otherwise dictated by the cancellation of the dipole moments on guanines.

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