Structure and Sequence Determinants Governing the Interactions of RNAs with Influenza A Virus Non-Structural Protein NS1

Autor:	Virginie Gaudon, Sascha Trapp, Emmanuel Kut, Franck Coste, Bertrand Castaing, Daniel Marc, A. Wacquiez
Přispěvatelé:	Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), REGION CENTRE-Val de Loire, France (RNApur project, 2015-00099396), Region Centre-Val de Loire (201600109193), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CASTAING, Bertrand
Rok vydání:	2020
Předmět:	0301 basic medicine Models Molecular non-structural NS1 RNA-protein interaction [SDV]Life Sciences [q-bio] viruses Mutant lcsh:QR1-502 Viral Nonstructural Proteins medicine.disease_cause 3D structure lcsh:Microbiology Influenza A Virus H1N1 Subtype RNA-Protein Interaction Interferon Influenza A virus 3' Untranslated Regions Genetics SELEX Aptamer Technique virus diseases RNA-Binding Proteins Aptamers Nucleotide 3. Good health [SDV] Life Sciences [q-bio] Infectious Diseases [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Influenza A Virus H7N1 Subtype RNA Viral Sequence motif medicine.drug Protein Binding Biology Article Cell Line 03 medical and health sciences Protein Domains Virology medicine Animals Humans influenza A virus RNA Messenger RNA Double-Stranded Messenger RNA 030102 biochemistry & molecular biology Base Sequence RNA 030104 developmental biology Nucleic acid Nucleic Acid Conformation
Zdroj:	Viruses Volume 12 Issue 9 Viruses, MDPI, 2020, 12 (9), pp.947. ⟨10.3390/v12090947⟩ Viruses, MDPI, 2020, 12 (9), 25 p. ⟨10.3390/v12090947⟩ Viruses, Vol 12, Iss 947, p 947 (2020) Viruses, 2020, 12 (9), 25 p. ⟨10.3390/v12090947⟩
ISSN:	1999-4915
DOI:	10.3390/v12090947⟩
Popis:	The non-structural protein NS1 of influenza A viruses is an RNA-binding protein of which its activities in the infected cell contribute to the success of the viral cycle, notably through interferon antagonism. We have previously shown that NS1 strongly binds RNA aptamers harbouring virus-specific sequence motifs (Marc et al., Nucleic Acids Res. 41, 434&ndash 449). Here, we started out investigating the putative role of one particular virus-specific motif through the phenotypic characterization of mutant viruses that were genetically engineered from the parental strain WSN. Unexpectedly, our data did not evidence biological importance of the putative binding of NS1 to this specific motif (UGAUUGAAG) in the 3&prime untranslated region of its own mRNA. Next, we sought to identify specificity determinants in the NS1-RNA interaction through interaction assays in vitro with several RNA ligands and through solving by X-ray diffraction the 3D structure of several complexes associating NS1&prime s RBD with RNAs of various affinities. Our data show that the RBD binds the GUAAC motif within double-stranded RNA helices with an apparent specificity that may rely on the sequence-encoded ability of the RNA to bend its axis. On the other hand, we showed that the RBD binds to the virus-specific AGCAAAAG motif when it is exposed in the apical loop of a high-affinity RNA aptamer, probably through a distinct mode of interaction that still requires structural characterization. Our data are consistent with more than one mode of interaction of NS1&prime s RBD with RNAs, recognizing both structure and sequence determinants.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a6a52e71a2c362b8ed359221ca21ad53 https://pubmed.ncbi.nlm.nih.gov/32867106 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.