Heat shock-induced SRSF10 dephosphorylation displays thermotolerance mediated by Hsp27.
Gene regulation in response to environmental stress is critical for the survival of all organisms. From Saccharomyces cerevisiae to humans, it has been observed that splicing of mRNA precursors is repressed upon heat shock. However, a mild heat pretreatment often prevents splicing inhibition in response to a subsequent and more severe heat shock, a phenomenon called splicing thermotolerance. We have shown previously that the splicing regulator SRSF10 (formerly SRp38) is specifically dephosphorylated by the phosphatase PP1 in response to heat shock and that dephosphorylated SRSF10 is responsible for splicing repression caused by heat shock. Here we report that a mild heat shock protects SRSF10 from dephosphorylation during a second and more severe heat shock. Furthermore, this "thermotolerance" of SRSF10 phosphorylation, like that of splicing, requires de novo protein synthesis, specifically the synthesis of heat shock proteins. Indeed, overexpression of one of these proteins, Hsp27, inhibits SRSF10 dephosphorylation in response to heat shock and does so by interaction with SRSF10. Our data thus provide evidence that splicing thermotolerance is acquired through maintenance of SRSF10 phosphorylation and that this is mediated at least in part by Hsp27.
Columbia University, Department of Biological Sciences, 1117 Fairchild Center, New York, NY 10027-7003, USA.
Yongsheng
Y
Shi
Kensei
K
Nishida
Dafne
D
Campigli Di Giammartino
James L
JL
Manley
D000222:Adaptation, Physiological; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D014176:Protein Biosynthesis; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D013696:Temperature
D018797:Cell Cycle Proteins; D055551:HSP27 Heat-Shock Proteins; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C115188:SRSF10 protein, human; D000068103:Serine-Arginine Splicing Factors