Unconventional miR-122 binding stabilizes the HCV genome by forming a trimolecular RNA structure

Nucleic Acids Res. 2013 Apr;41(7):4230-40. doi: 10.1093/nar/gkt075. Epub 2013 Feb 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions*
  • Base Pairing
  • Base Sequence
  • Binding Sites
  • Exoribonucleases / metabolism
  • Genome, Viral
  • Hepacivirus / genetics*
  • Humans
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • RNA, Viral / chemistry*
  • RNA, Viral / metabolism


  • 5' Untranslated Regions
  • MIRN122 microRNA, human
  • MicroRNAs
  • RNA, Viral
  • Exoribonucleases