Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock

Chanseok Shin, Ying Feng and James L. Manley ()
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Chanseok Shin: Columbia University
Ying Feng: Columbia University
James L. Manley: Columbia University

Nature, 2004, vol. 427, issue 6974, 553-558

Abstract: Abstract The cellular response to stresses such as heat shock involves changes in gene expression1. It is well known that the splicing of messenger RNA precursors is generally repressed on heat shock2,3, but the factors responsible have not been identified4,5,6,7,8. SRp38 is an SR protein splicing factor9,10 that functions as a general repressor of splicing. It is activated by dephosphorylation and required for splicing repression in M-phase cells11. Here we show that SRp38 is also dephosphorylated on heat shock and that this dephosphorylation correlates with splicing inhibition. Notably, depletion of SRp38 from heat-shocked cell extracts derepresses splicing, and adding back dephosphorylated SRp38 specifically restores inhibition. We further show that dephosphorylated SRp38 interacts with a U1 small nuclear ribonucleoprotein particle (snRNP) protein, and that this interaction interferes with 5′-splice-site recognition by the U1 snRNP. Finally, SRp38-deficient DT40 cells show an altered cell-cycle profile consistent with a mitotic defect; they are also temperature sensitive and defective in recovery after heat shock. SRp38 thus plays a crucial role in cell survival under stress conditions by inhibiting the splicing machinery.

Date: 2004
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DOI: 10.1038/nature02288

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