Cell Host & Microbe
Volume 4, Issue 1, 17 July 2008, Pages 77-85
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Article
Position-Dependent Function for a Tandem MicroRNA miR-122-Binding Site Located in the Hepatitis C Virus RNA Genome

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Summary

MicroRNAs usually interact with 3′ noncoding regions (3′NCRs) of target mRNAs leading to downregulation of mRNA expression. In contrast, liver-specific microRNA miR-122 interacts with the 5′ end of the hepatitis C virus RNA genome, resulting in increased viral RNA abundance. We find that inserting the viral miR-122 binding site into the 3′ noncoding region of a reporter mRNA leads to downregulation of mRNA expression, indicating that the location of the miR-122 binding site dictates its effect on gene regulation. Furthermore, we discovered an adjacent, second miR-122 binding site, separated from the first by a highly conserved 14-nucleotide sequence. Mutational analysis demonstrates that both miR-122 binding sites in a single viral genome are occupied by the microRNA and function cooperatively to regulate target gene expression. These findings set a paradigm for dual, position-dependent functions of tandem microRNA-binding sites. Targeting an oligomeric microRNA complex offers potential as an antiviral-intervention strategy.

MICROBIO
RNA

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These authors contributed equally to this work