title: Widespread inhibition of posttranscriptional splicing shapes the cellular transcriptome following heat shock.
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.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Reut
authors.initials: R
authors.lastname: Shalgi
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hurt
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Lindquist
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: cburge@mit.edu.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics; D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D018869:Heat-Shock Response; D007438:Introns; D051379:Mice; D010084:Oxidation-Reduction; D017510:Protein Folding; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D017381:Spliceosomes / Q000235:genetics; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D022661:RNA, Untranslated; D000604:Amino Acyl-tRNA Synthetases