| Literature DB >> 25768906 |
Joseph M Luna1, Troels K H Scheel2, Tal Danino3, Katharina S Shaw4, Aldo Mele5, John J Fak5, Eiko Nishiuchi4, Constantin N Takacs6, Maria Teresa Catanese4, Ype P de Jong7, Ira M Jacobson8, Charles M Rice9, Robert B Darnell10.
Abstract
Hepatitis C virus (HCV) uniquely requires the liver-specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (AGO) during HCV infection showed robust AGO binding on the HCV 5'UTR at known and predicted miR-122 sites. On the human transcriptome, we observed reduced AGO binding and functional mRNA de-repression of miR-122 targets during virus infection. This miR-122 "sponge" effect was relieved and redirected to miR-15 targets by swapping the miRNA tropism of the virus. Single-cell expression data from reporters containing miR-122 sites showed significant de-repression during HCV infection depending on expression level and site number. We describe a quantitative mathematical model of HCV-induced miR-122 sequestration and propose that such miR-122 inhibition by HCV RNA may result in global de-repression of host miR-122 targets, providing an environment fertile for the long-term oncogenic potential of HCV.Entities:
Mesh：
Substances：
Year: 2015 PMID： 25768906 PMCID： PMC4386883 DOI： 10.1016/j.cell.2015.02.025
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582