HCV RNA acts as a miR-122 sponge

The liver-specific microRNA-122 (miR-122) represses translation by associating with Argonaute and binding to cellular mRNAs (ceRNAs). Notably, replication of hepatitis C virus (HCV) requires binding of miR-122 to viral genomic RNA. Now, Luna et al. show that extensive binding of miR-122 to the viral RNA results in reduced binding of miR-122 to ceRNAs, which leads to functional de-repression of its endogenous mRNA targets in HCV-infected cells. To test the hypothesis that HCV RNA acts as a sponge that sequesters miR-122 away from its cellular targets, the authors modified the miR-122-binding sites in the viral RNA to bind miR-15. Indeed, infection with this viral variant resulted in de-repression of miR-15 ceRNAs, whereas miR-122 targets were unaffected. These data suggest that HCV modifies the functions of infected cells by sequestering a key host microRNA.