Transcriptomics

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Hepatitis C virus functionally sequesters miR-122 [miR-122 KO vs Control CLIP]


ABSTRACT: 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 could be 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 number of sites. 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. AGO HITS-CLIP libraries were generated from single cell clones of miR-122 deleted Huh7.5 cells using CRISPR (KO), unedited controls (WT), or cells transfected with GFP instead of CRISPR. Libraries were generated with a 4nt index read, a common priming sequence, followed by a 5nt degenerate barcode terminiating in a G. Files have been demultiplexed such that the 5nt degenerate barcode has been appended as the first 5 nucleotides of the read.

ORGANISM(S): Homo sapiens  

SUBMITTER: Robert B Darnell  Ira M Jacobson   Eiko Nishiuchi   Aldo Mele   John J Fak   Charles M Rice   Maria T Catanese   Constantin N Takacs   Katharina S Shaw   Joseph M Luna   Tal Danino   Troels K Scheel   Ype P de Jong    

PROVIDER: E-GEOD-64679 | ArrayExpress | 2015-01-06

SECONDARY ACCESSION(S): GSE64679SRP051708PRJNA271612

REPOSITORIES: GEO, ArrayExpress, ENA

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