microRNA-122 stimulates translation of hepatitis C virus RNA

Hepatitis C virus (HCV) is a positive strand RNA virus that propagates primarily in the liver. We show here that the liver‐specific microRNA‐122 (miR‐122), a member of a class of small cellular RNAs that mediate post‐transcriptional gene regulation usually by repressing the translation of mRNAs through interaction with their 3′‐untranslated regions (UTRs), stimulates the translation of HCV. Sequestration of miR‐122 in liver cell lines strongly reduces HCV translation, whereas addition of miR‐122 stimulates HCV translation in liver cell lines as well as in the non‐liver HeLa cells and in rabbit reticulocyte lysate. The stimulation is conferred by direct interaction of miR‐122 with two target sites in the 5′‐UTR of the HCV genome. With a replication‐defective NS5B polymerase mutant genome, we show that the translation stimulation is independent of viral RNA synthesis. miR‐122 stimulates HCV translation by enhancing the association of ribosomes with the viral RNA at an early initiation stage. In conclusion, the liver‐specific miR‐122 may contribute to HCV liver tropism at the level of translation.

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