Hepatitis C virus RNA functionally sequesters miR-122 #MMPMID25768906
Luna JM; Scheel TKH; Danino T; Shaw KS; Mele A; Fak JJ; Nishiuchi E; Takacs CN; Catanese MT; de Jong YP; Jacobson IM; Rice CM; Darnell RB
Cell 2015[Mar]; 160 (6): 1099-110 PMID25768906show ga
Hepatitis C virus 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.
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Cell 2015 ; 160 (6): 1099-110
