title: miR-122 and the Hepatitis C RNA genome: more than just stability.
abstract: MicroRNA-122 (miR-122) plays a key role in hepatitis C virus (HCV) replication, but understanding exactly how it functions in the viral lifecycle has been elusive. HCV is a positive-strand virus with a messenger-sense RNA genome, to which miR-122 binds in a non-canonical fashion at two sites near the 5' end. Recent studies show that miR-122 recruits Ago-2 to the genomic RNA, stabilizing it and slowing its decay in infected cells. This led us to investigate decay pathways that mediate degradation of the viral RNA. We found HCV RNA is degraded primarily by the cytoplasmic 5' exonuclease Xrn1 in infected cells. miR-122 lost its stabilizing effect when cells were depleted of Xrn1 using an RNAi strategy, providing strong evidence that miR-122 acts to protect the viral RNA from Xrn1-mediated 5' exonucleolytic decay. However, Xrn1 depletion did not rescue replication of a viral mutant defective in miR-122 binding, indicating that there is much more to miR-122's actions than prevention of Xrn1 decay. Here, we consider the role of miR-122 in the viral lifecycle, and explore the possibility that it might function directly in viral RNA synthesis.
authors.affiliation: Department of Medicine, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.forename: Takahiro
authors.initials: T
authors.lastname: Masaki
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Lemon
mesh_terms: D020121:5' Untranslated Regions; D045744:Cell Line, Tumor; D005092:Exonucleases / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral; D005092:Exonucleases
keywords: PCBP2; RNA decay; RNA stability; Xrn1; hepatitis C virus; micro-RNA; replication; translation