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Series GSE70481 Query DataSets for GSE70481
Status Public on Jul 23, 2015
Title Viral nucleases reveal an mRNA degradation-transcription feedback loop in mammalian cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Gamma-herpesviruses encode a cytoplasmic mRNA-targeting endonuclease, termed SOX, that cleaves the majority of mRNAs within a cell. Cleaved fragments are subsequently degraded by the cellular mRNA degradation machinery. Here, we reveal that mammalian cells respond to this widespread cytoplasmic mRNA decay by altering levels of RNA polymerase II (RNAPII) transcription in the nucleus. Measurements of both RNAPII recruitment to promoters and nascent mRNA synthesis revealed that the majority of affected genes are transcriptionally repressed in SOX-expressing cells. The transcriptional feedback does not occur in response to the initial endonuclease-induced cleavage, but instead to degradation of the cleaved fragments by cellular exonucleases. In particular, Xrn1 catalytic activity is required for transcriptional repression. Notably, viral mRNA transcription escapes decay-induced repression, and this escape requires Xrn1. Collectively, these results indicate that mRNA decay rates impact transcription in mammalian cells, and that gamma-herpesviruses have incorporated this feedback mechanism into their own gene expression strategy.
 
Overall design NIH 3T3 cells were mock, WT, or ∆HS infected with MHV68 in duplicate and 4sU-labeled RNA isolated. 4sU-labeled RNA was submitted for sequencing and reads aligned to the mouse genome or MHV68 viral genome. Differential cellular gene expression was determined between mock and WT infected, mock and ∆HS infected, as well as differential viral gene expression between WT and ∆HS.
 
Contributor(s) Abernathy E, Glaunsinger B, Alla R
Citation(s) 26211836
Submission date Jul 02, 2015
Last update date May 15, 2019
Contact name Britt Glaunsinger
Organization name UC Berkeley
Department Plant and Microbiology
Street address 565 Li Ka Shing Center
City Berkeley
State/province California
ZIP/Postal code 94720
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (6)
GSM1782681 mock rep1
GSM1782682 mock rep2
GSM1782683 MHV68 WT infection rep1
Relations
BioProject PRJNA288804
SRA SRP060247

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
GSE70481_RAW.tar 550.0 Kb (http)(custom) TAR (of TXT)
GSE70481_ViralGenes_deltaHSvWT.xls.gz 4.2 Kb (ftp)(http) XLS
GSE70481_WTvMock.xls.gz 571.2 Kb (ftp)(http) XLS
GSE70481_deltaHSvMock.xls.gz 542.5 Kb (ftp)(http) XLS
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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