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Science 309 (5740): 1577-1581

Copyright © 2005 by the American Association for the Advancement of Science

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 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.

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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