Transcriptomics

Dataset Information

96

A broad RNA virus survey reveals dependence on host miRNAs and specific sequestration modulating the cellular transcriptome


ABSTRACT: Small non-coding RNAs have emerged as key players in modulation of viral infection. A unique example is the critical dependence of hepatitis C virus (HCV) on the liver-specific microRNA (miRNA), miR-122, which has surfaced as therapeutic target. Here, we used crosslinking immunoprecipitation (CLIP) of the Argonaute (AGO) protein to characterize strengths and specificities of miRNA interactions across 15 viral genomes. Intriguingly, replication of pestiviruses, which are major threats to milk and meat industry, critically depends on cellular miR-17 and let-7 interactions with the viral 3’UTR. Like HCV, miRNA binding enhanced translation and prevented viral RNA degradation. On the cellular transcriptome, pestiviral miR-17 sequestration in vitro and ex vivo conferred reduced AGO binding and functional mRNA de-repression for miR-17 targets. These findings generalize the concept of RNA virus dependence on cellular miRNAs, highlight such interactions as therapeutic targets, and connect functional regulation of the transcriptome in primary cells to miRNA sequestration. Several subseries of analyses were performed. For each sample, subseries to which it belongs are indicated. In the “Virus AGO-CLIP” subseries, AGO-CLIP was performed on cells infected with virus as indicated. Processed reads were aligned to the host genome (hg18 or BosTau7) and to the respective viral genome. The primary data of interest from this subseries concerns AGO binding to viral RNA, and is given as processed data file “Table S1”. In the “Virus AGO-CLIP: BVDV vs. Mock” subseries, AGO-CLIP was performed on four replicates each of BVDV and mock infected MDBK cells. CLIP reads aligned to BosTau7 were clustered, and differential analysis was performed on binding to each cluster. In addition, differential analysis of AGO bound miRNAs was performed. The associated data is given as processed data file “Table S3 and S4”. In the “AGO-CLIP: tinyLNA-17 vs. Mock” AGO-CLIP was performed on four replicates each of tinyLNA-17 and mock treated MDBK cells. CLIP reads aligned to BosTau7 were clustered, and differential analysis was performed on binding to each cluster. The associated data is given as processed data file “Table S5”. In the “RNA-seq: BVDV vs. Mock” subseries, mRNA-seq was performed on two replicates each of MDBK cells infected with different biotypes of BVDV or with miR-17 seed site mutant BVDV. The latter (incl. mock controls) were trans-complemented with the corresponding mutated miR-17. Differential gene expression analysis was performed between selected conditions. The associated data is given as processed data file “Table S6”.

REANALYSIS of: GSE64676

SUBMITTER: Robert B Darnell  Eiko Nishiuchi   Rémy Bruggmann   Irene Keller   Kathryn Rozen-Gagnon   Amir Shlomai   Charles M Rice   Markus Gerber   Matthias Liniger   Troels K H Scheel   Gaël Auray   Troels K Scheel   John Fak   Joseph M Luna   Nicolas Ruggli    

PROVIDER: E-GEOD-76967 | ArrayExpress | 2016-02-17

SECONDARY ACCESSION(S): GSE76967SRP068577PRJNA309153

REPOSITORIES: GEO, ArrayExpress, ENA

altmetric image

Publications

Sorry, this publication's infomation has not been loaded in the Indexer, please go directly to PUBMED or Altmetric.

Similar Datasets

2014-08-13 | E-GEOD-56180 | ArrayExpress
2014-12-10 | E-GEOD-59909 | ArrayExpress
2013-08-22 | E-GEOD-43747 | ArrayExpress
2015-06-04 | E-GEOD-69169 | ArrayExpress
2014-05-30 | E-GEOD-52082 | ArrayExpress
2015-01-28 | E-GEOD-64677 | ArrayExpress
2013-05-09 | E-GEOD-40468 | ArrayExpress
2011-10-18 | E-GEOD-1291 | ArrayExpress
2014-05-03 | E-GEOD-39911 | ArrayExpress
2009-05-30 | GSE16338 | GEO