title: miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components.
abstract: In animals, microRNAs (miRNAs) generally repress gene expression by binding to sites in the 3'-untranslated region (UTR) of target mRNAs. miRNAs have also been reported to repress or activate gene expression by binding to 5'-UTR sites, but the extent of such regulation and the factors that govern these different responses are unknown. Liver-specific miR-122 binds to sites in the 5'-UTR of hepatitis C virus (HCV) RNA and positively regulates the viral life cycle, in part by stimulating HCV translation. Here, we characterize the features that allow miR-122 to activate translation via the HCV 5'-UTR. We find that this regulation is a highly specialized process that requires uncapped RNA, the HCV internal ribosome entry site (IRES) and the 3' region of miR-122. Translation activation does not involve a previously proposed structural transition in the HCV IRES and is mediated by Argonaute proteins. This study provides an important insight into the requirements for the miR-122-HCV interaction, and the broader consequences of miRNAs binding to 5'-UTR sites.
authors.affiliation: Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Ashley P E
authors.initials: AP
authors.lastname: Roberts
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lewis
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Jopling
mesh_terms: D020121:5' Untranslated Regions; D060565:Argonaute Proteins / Q000502:physiology; D001665:Binding Sites; D002460:Cell Line; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D016366:Open Reading Frames; D010442:Peptide Chain Initiation, Translational; D012314:RNA Cap Analogs / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D060565:Argonaute Proteins; D035683:MicroRNAs; D012314:RNA Cap Analogs; D012367:RNA, Viral