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Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific MicroRNA
Catherine L. Jopling,1
MinKyung Yi,2
Alissa M. Lancaster,1
Stanley M. Lemon,2
Peter Sarnow1*
Abstract:
MicroRNAs are small RNA molecules that regulate messenger RNA(mRNA) expression. MicroRNA 122 (miR-122) is specifically expressedand highly abundant in the human liver. We show that the sequestrationof miR-122 in liver cells results in marked loss of autonomouslyreplicating hepatitis C viral RNAs. A genetic interaction betweenmiR-122 and the 5' noncoding region of the viral genome wasrevealed by mutational analyses of the predicted microRNA bindingsite and ectopic expression of miR-122 molecules containingcompensatory mutations. Studies with replication-defective RNAssuggested that miR-122 did not detectably affect mRNA translationor RNA stability. Therefore, miR-122 is likely to facilitatereplication of the viral RNA, suggesting that miR-122 may presenta target for antiviral intervention.
1 Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. 2 Center for Hepatitis Research, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1019, USA.
* To whom correspondence should be addressed. E-mail: psarnow{at}stanford.edu
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