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Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA.

Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P.

Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.

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.

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PMID: 16141076 [PubMed - indexed for MEDLINE]