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Series GSE76967 Query DataSets for GSE76967
Status Public on Jan 20, 2016
Title A broad RNA virus survey reveals dependence on host miRNAs and specific sequestration modulating the cellular transcriptome
Organisms Homo sapiens; Bos taurus
Experiment type Expression profiling by high throughput sequencing
Other
Third-party reanalysis
Summary 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.
 
Overall design 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”.
 
Contributor(s) Scheel TK, Luna JM, Liniger M, Nishiuchi E, Rozen-Gagnon K, Shlomai A, Auray G, Gerber M, Fak J, Keller I, Bruggmann R, Darnell RB, Ruggli N, Rice CM
Citation(s) 26962949
Submission date Jan 19, 2016
Last update date May 15, 2019
Contact name Troels K H Scheel
E-mail(s) tscheel@sund.ku.dk
Organization name University of Copenhagen
Department Institute for Immunology and Microbiology
Lab Copenhagen Hepatitis C Program (CO-HEP)
Street address Blegdamsvej 3
City Copenhagen N
State/province Copenhagen
ZIP/Postal code 2200
Country Denmark
 
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL15749 Illumina HiSeq 2000 (Bos taurus)
Samples (103)
GSM2041566 JL0096.1_CLIP-seq_Huh-7.5_HCVwt
GSM2041567 JL0096.2_CLIP-seq_Huh-7.5_HCVwt
GSM2041568 JL0096.3_CLIP-seq_Huh-7.5_HCVwt
Relations
BioProject PRJNA309153
SRA SRP068577

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE76967_Table_S1.txt.gz 11.1 Mb (ftp)(http) TXT
GSE76967_Table_S3.xlsx.gz 73.3 Kb (ftp)(http) XLSX
GSE76967_Table_S4.txt.gz 4.3 Mb (ftp)(http) TXT
GSE76967_Table_S5.txt.gz 2.5 Mb (ftp)(http) TXT
GSE76967_Table_S6.txt.gz 1.0 Mb (ftp)(http) TXT
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Processed data are available on Series record
Raw data are available in SRA
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