G-Quadruplexes in RNA Biology: Recent Advances and Future Directions

Dumas, Lucie; Herviou, Pauline; Dassi, Erik; Cammas, Anne; Millevoi, Stefania

doi:10.1016/j.tibs.2020.11.001

Cited by 122 publications

(108 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…G4s regulate major eukaryotic cell processes and are enriched in key regulatory regions of their genomes and transcriptomes including telomeres, promoters and 5′UTR of highly transcribed genes ( 20 , 21 ). While DNA G4s regulate the transcription of a number of human genes, especially oncogenes, RNA G4s participate in several mechanisms linked with mRNA metabolism, such as their translation, splicing, stability, polyadenylation and localization ( 22 , 23 ). G4s are also present in the genomes of DNA and RNA viruses and control critical steps of their replication ( 24–27 ).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction

Lavigne

Helynck

Rigolet

et al. 2021

Nucleic Acids Research

View full text Add to dashboard Cite

The multidomain non-structural protein 3 (Nsp3) is the largest protein encoded by coronavirus (CoV) genomes and several regions of this protein are essential for viral replication. Of note, SARS-CoV Nsp3 contains a SARS-Unique Domain (SUD), which can bind Guanine-rich non-canonical nucleic acid structures called G-quadruplexes (G4) and is essential for SARS-CoV replication. We show herein that the SARS-CoV-2 Nsp3 protein also contains a SUD domain that interacts with G4s. Indeed, interactions between SUD proteins and both DNA and RNA G4s were evidenced by G4 pull-down, Surface Plasmon Resonance and Homogenous Time Resolved Fluorescence. These interactions can be disrupted by mutations that prevent oligonucleotides from folding into G4 structures and, interestingly, by molecules known as specific ligands of these G4s. Structural models for these interactions are proposed and reveal significant differences with the crystallographic and modeled 3D structures of the SARS-CoV SUD-NM/G4 interaction. Altogether, our results pave the way for further studies on the role of SUD/G4 interactions during SARS-CoV-2 replication and the use of inhibitors of these interactions as potential antiviral compounds.

show abstract

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction

Lavigne

Helynck

Rigolet

et al. 2021

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Finally, pieces of evidence have shown that G4 structures may be relevant also in the RNA world [ 20 ]. Indeed, RNA regions, such as the 5’-untranslated regions (5’-UTR) [ 11 ], or RNA species, including long non-coding RNAs (lncRNAs) [ 21 ], have been found to be enriched in quadruplex-forming sequences. This evidence indicates that RNA G4 may play an important regulatory role at post-transcriptional level, where they can operate in cis or in trans to control the coding capacity of the genome [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, RNA regions, such as the 5’-untranslated regions (5’-UTR) [ 11 ], or RNA species, including long non-coding RNAs (lncRNAs) [ 21 ], have been found to be enriched in quadruplex-forming sequences. This evidence indicates that RNA G4 may play an important regulatory role at post-transcriptional level, where they can operate in cis or in trans to control the coding capacity of the genome [ 20 , 21 ]. Specifically, G4 structures located in the proximity of splicing sites can act as cis -regulatory elements during the splicing reaction of a number of genes, including the tumor suppressor TP53 and the human telomerase reverse transcriptase TERT [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Alessandrini

Recagni

Zaffaroni

et al. 2021

IJMS

View full text Add to dashboard Cite

Nucleic acid sequences able to adopt a G-quadruplex conformation are overrepresented within the human genome. This evidence strongly suggests that these genomic regions have been evolutionary selected to play a pivotal role in several aspects of cell biology. In the present review article, we provide an overview on the biological impact of targeting G-quadruplexes in cancer. A variety of small molecules showing good G-quadruplex stabilizing properties has been reported to exert an antitumor activity in several preclinical models of human cancers. Moreover, promiscuous binders and multiple targeting G-quadruplex ligands, cancer cell defense responses and synthetic lethal interactions of G-quadruplex targeting have been also highlighted. Overall, evidence gathered thus far indicates that targeting G-quadruplex may represent an innovative and fascinating therapeutic approach for cancer. The continued methodological improvements, the development of specific tools and a careful consideration of the experimental settings in living systems will be useful to deepen our knowledge of G-quadruplex biology in cancer, to better define their role as therapeutic targets and to help design and develop novel and reliable G-quadruplex-based anticancer strategies.

show abstract

“…In yeast and human, G4s are enriched in telomeric and ribosomal DNA, at transcriptional regulatory units, and at mitotic and meiotic double-strand break sites [53,55,56]. G4s can also form in RNA, where they can affect its stability or translation [57][58][59][60].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, contemporary research has demonstrated the importance of G4s in various cellular processes, including interactions with TFs [60][61][62][63]. Moreover, the targeting of the unique structure of G4s is proposed as a good tool for various diseases therapies including cancer [64][65][66][67][68].…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay

Monti

Brázda

Bohálová

et al. 2021

Genes

View full text Add to dashboard Cite

P53, P63, and P73 proteins belong to the P53 family of transcription factors, sharing a common gene organization that, from the P1 and P2 promoters, produces two groups of mRNAs encoding proteins with different N-terminal regions; moreover, alternative splicing events at C-terminus further contribute to the generation of multiple isoforms. P53 family proteins can influence a plethora of cellular pathways mainly through the direct binding to specific DNA sequences known as response elements (REs), and the transactivation of the corresponding target genes. However, the transcriptional activation by P53 family members can be regulated at multiple levels, including the DNA topology at responsive promoters. Here, by using a yeast-based functional assay, we evaluated the influence that a G-quadruplex (G4) prone sequence adjacent to the p53 RE derived from the apoptotic PUMA target gene can exert on the transactivation potential of full-length and N-terminal truncated P53 family α isoforms (wild-type and mutant). Our results show that the presence of a G4 prone sequence upstream or downstream of the P53 RE leads to significant changes in the relative activity of P53 family proteins, emphasizing the potential role of structural DNA features as modifiers of P53 family functions at target promoter sites.

show abstract

G-Quadruplexes in RNA Biology: Recent Advances and Future Directions

Cited by 122 publications

References 119 publications

SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction

SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay

Contact Info

Product

Resources

About