RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand

Abstract DNA and RNA guanine-rich oligonucleotides can form non-canonical structures called G-quadruplexes or “G4” that are based on the stacking of G-quartets. The role of DNA and RNA G4 is documented in eukaryotic cells and in pathogens such as viruses. Yet, G4 have been identified only in a few R...

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Autores principales:	Chloé Jaubert, Amina Bedrat, Laura Bartolucci, Carmelo Di Primo, Michel Ventura, Jean-Louis Mergny, Samir Amrane, Marie-Line Andreola
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/748f46532b7141e4bbf232f943511c9d
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spelling	oai:doaj.org-article:748f46532b7141e4bbf232f943511c9d2021-12-02T15:07:58ZRNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand10.1038/s41598-018-26582-32045-2322https://doaj.org/article/748f46532b7141e4bbf232f943511c9d2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-26582-3https://doaj.org/toc/2045-2322Abstract DNA and RNA guanine-rich oligonucleotides can form non-canonical structures called G-quadruplexes or “G4” that are based on the stacking of G-quartets. The role of DNA and RNA G4 is documented in eukaryotic cells and in pathogens such as viruses. Yet, G4 have been identified only in a few RNA viruses, including the Flaviviridae family. In this study, we analysed the last 157 nucleotides at the 3′end of the HCV (−) strand. This sequence is known to be the minimal sequence required for an efficient RNA replication. Using bioinformatics and biophysics, we identified a highly conserved G4-prone sequence located in the stem-loop IIy’ of the negative strand. We also showed that the formation of this G-quadruplex inhibits the in vitro RNA synthesis by the RdRp. Furthermore, Phen-DC3, a specific G-quadruplex binder, is able to inhibit HCV viral replication in cells in conditions where no cytotoxicity was measured. Considering that this domain of the negative RNA strand is well conserved among HCV genotypes, G4 ligands could be of interest for new antiviral therapies.Chloé JaubertAmina BedratLaura BartolucciCarmelo Di PrimoMichel VenturaJean-Louis MergnySamir AmraneMarie-Line AndreolaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chloé Jaubert Amina Bedrat Laura Bartolucci Carmelo Di Primo Michel Ventura Jean-Louis Mergny Samir Amrane Marie-Line Andreola RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand
description	Abstract DNA and RNA guanine-rich oligonucleotides can form non-canonical structures called G-quadruplexes or “G4” that are based on the stacking of G-quartets. The role of DNA and RNA G4 is documented in eukaryotic cells and in pathogens such as viruses. Yet, G4 have been identified only in a few RNA viruses, including the Flaviviridae family. In this study, we analysed the last 157 nucleotides at the 3′end of the HCV (−) strand. This sequence is known to be the minimal sequence required for an efficient RNA replication. Using bioinformatics and biophysics, we identified a highly conserved G4-prone sequence located in the stem-loop IIy’ of the negative strand. We also showed that the formation of this G-quadruplex inhibits the in vitro RNA synthesis by the RdRp. Furthermore, Phen-DC3, a specific G-quadruplex binder, is able to inhibit HCV viral replication in cells in conditions where no cytotoxicity was measured. Considering that this domain of the negative RNA strand is well conserved among HCV genotypes, G4 ligands could be of interest for new antiviral therapies.
format	article
author	Chloé Jaubert Amina Bedrat Laura Bartolucci Carmelo Di Primo Michel Ventura Jean-Louis Mergny Samir Amrane Marie-Line Andreola
author_facet	Chloé Jaubert Amina Bedrat Laura Bartolucci Carmelo Di Primo Michel Ventura Jean-Louis Mergny Samir Amrane Marie-Line Andreola
author_sort	Chloé Jaubert
title	RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand
title_short	RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand
title_full	RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand
title_fullStr	RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand
title_full_unstemmed	RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand
title_sort	rna synthesis is modulated by g-quadruplex formation in hepatitis c virus negative rna strand
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/748f46532b7141e4bbf232f943511c9d
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RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand

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