title: Unconventional miR-122 binding stabilizes the HCV genome by forming a trimolecular RNA structure.
abstract: MicroRNAs (miRNAs) typically downregulate protein expression from target mRNAs through limited base-pairing interactions between the 5' 'seed' region of the miRNA and the mRNA 3' untranslated region (3'UTR). In contrast to this established mode of action, the liver-specific human miR-122 binds at two sites within the hepatitis C viral (HCV) 5'UTR, leading to increased production of infectious virions. We show here that two copies of miR-122 interact with the HCV 5'UTR at partially overlapping positions near the 5' end of the viral transcript to form a stable ternary complex. Both miR-122 binding sites involve extensive base pairing outside of the seed sequence; yet, they have substantially different interaction affinities. Structural probing reveals changes in the architecture of the HCV 5'UTR that occur on interaction with miR-122. In contrast to previous reports, however, results using both the recombinant cytoplasmic exonuclease Xrn1 and liver cell extracts show that miR-122-mediated protection of the HCV RNA from degradation does not correlate with stimulation of viral propagation in vivo. Thus, the miR-122:HCV ternary complex likely functions at other steps critical to the viral life cycle.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors: Stefanie A
authors: SA
authors: Mortimer
authors: Jennifer A
authors: JA
authors: Doudna
mesh_terms: D020121:5' Untranslated Regions; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D005095:Exoribonucleases / Q000378:metabolism; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral; D005095:Exoribonucleases