Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific MicroRNA

Science. 2005 Sep 2;309(5740):1577-81. doi: 10.1126/science.1113329.

Abstract

MicroRNAs are small RNA molecules that regulate messenger RNA (mRNA) expression. MicroRNA 122 (miR-122) is specifically expressed and highly abundant in the human liver. We show that the sequestration of miR-122 in liver cells results in marked loss of autonomously replicating hepatitis C viral RNAs. A genetic interaction between miR-122 and the 5' noncoding region of the viral genome was revealed by mutational analyses of the predicted microRNA binding site and ectopic expression of miR-122 molecules containing compensatory mutations. Studies with replication-defective RNAs suggested that miR-122 did not detectably affect mRNA translation or RNA stability. Therefore, miR-122 is likely to facilitate replication of the viral RNA, suggesting that miR-122 may present a target for antiviral intervention.

Publication types

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

MeSH terms

  • Animals
  • Base Pairing
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Gene Expression Regulation
  • Hepacivirus / genetics*
  • Humans
  • Liver / metabolism*
  • Liver / virology*
  • Mice
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Molecular Sequence Data
  • Mutation
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*

Substances

  • MicroRNAs
  • RNA, Messenger
  • RNA, Viral