Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock
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Burge_Widespread inhibition.pdf
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Author(s)
Shalgi, Reut
Hurt, Jessica A.
Lindquist, Susan
Burge, Christopher B
Date Issued
May 2014
Journal
Cell Reports
Publisher
Elsevier
Citation
Shalgi, Reut, Jessica A. Hurt, Susan Lindquist, and Christopher B. Burge. “Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome Following Heat Shock.” Cell Reports 7, no. 5 (June 2014): 1362–1370.
Version
Final published version
Abstract
During heat shock and other proteotoxic stresses, cells regulate multiple steps in gene expression in order to globally repress protein synthesis and selectively upregulate stress response proteins. Splicing of several mRNAs is known to be inhibited during heat stress, often meditated by SRp38, but the extent and specificity of this effect have remained unclear. Here, we examined splicing regulation genome-wide during heat shock in mouse fibroblasts. We observed widespread retention of introns in transcripts from ~1,700 genes, which were enriched for tRNA synthetase, nuclear pore, and spliceosome functions. Transcripts with retained introns were largely nuclear and untranslated. However, a group of 580+ genes biased for oxidation reduction and protein folding functions continued to be efficiently spliced. Interestingly, these unaffected transcripts are mostly cotranscriptionally spliced under both normal and stress conditions, whereas splicing-inhibited transcripts are mostly spliced posttranscriptionally. Altogether, our data demonstrate widespread repression of splicing in the mammalian heat stress response, disproportionately affecting posttranscriptionally spliced genes.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2014.04.044
