Heat shock-induced SRSF10 dephosphorylation displays thermotolerance mediated by Hsp27.
Heat shock-induced SRSF10 dephosphorylation displays thermotolerance mediated by Hsp27.
复制标题
热休克诱导的 SRSF10 去磷酸化表现出由 Hsp27 介导的耐热性。
DOI：
10.1128/mcb.01123-10
复制
发表时间：
2011
影响因子：
5.3
通讯作者：
Manley,JamesL
中科院分区：
文献类型：
--
作者：
Shi,Yongsheng;Nishida,Kensei;CampigliDiGiammartino,Dafne;Manley,JamesL
对环境胁迫作出反应的基因调控对所有生物的生存至关重要。从酿酒酵母到人类，人们已经观察到在热休克时，mRNA前体的剪接受到抑制。然而，温和的热预处理通常会防止剪接抑制，以应对随后更严重的热冲击，这种现象称为剪接耐热性。我们以前已经证明，剪接调节因子SRSF10(以前的SRp38)是由磷酸酶PP1特异性地在热休克反应中去磷酸化的，而去磷酸化的SRSF10负责热休克引起的剪接抑制。在这里，我们报告说，温和的热休克保护SRSF10在第二次和更严重的热休克中不会去磷酸化。此外，SRSF10磷酸化的这种“耐热性”，就像剪接一样，需要从头合成蛋白质，特别是热休克蛋白质的合成。事实上，其中一种蛋白质Hsp27的过表达抑制了SRSF10在热休克时的去磷酸化，并通过与SRSF10的相互作用来实现这一点。因此，我们的数据提供了证据，证明剪接耐热性是通过维持SRSF10的磷酸化而获得的，这至少部分是由Hsp27介导的。
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.