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

Abstract

The cellular response to stresses such as heat shock involves changes in gene expression. It is well known that the splicing of messenger RNA precursors is generally repressed on heat shock, but the factors responsible have not been identified. SRp38 is an SR protein splicing factor that functions as a general repressor of splicing. It is activated by dephosphorylation and required for splicing repression in M-phase cells. 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.

BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells

“…As BCLAF1 is a highly conserved gene between human and chicken, changes of exon 5a were also observed in chicken cell lines depleted of SRSF10 (ref. 30) (Supplementary Fig. 6b).…”

Triagem funcional de genes envolvidos no processo de manutenção da inativação do cromossomo X em humanos

“…Quando super-expresso antagoniza a atividade das proteínas SR SF2/ASF e SC35. Shin et al, 2004;Fushimi et al, 2005;Shin et al, 2005;Shi & Manley, 2007;Biamonti & Caceres, 2009;Feng et al, 2009;Xiao et al, 2011. Hao et al, 1997;Kawanishi et al, 2000;Schoch et al, 2001;Bonanomi et al, 2007;Prescott et al, 2009;Lin & Sun, 2011;Bogan, 2012. Cisternas et al, 2003;Sadakata et al, 2007;Corpet et al, 2011; 2012. Também expresso no feto sendo importante para seu crescimento e desenvolvimento e para crescimento pós-natal normal.…”

“…A proteína SRSF10 é uma proteína do tipo SR (fator de splicing não-snRNP que contém domínios ricos em serina e arginina) que participa da regulação de splicing constitutivo e alternativo (Shin et al, 2004;Shi et al, 2005;Feng et al, 2009). Sua atividade é regulada principalmente por fosforilação.…”

“…Sua atividade é regulada principalmente por fosforilação. Embora geralmente atue em sua forma desfosforilada como repressor geral de splicing (Shin & Manley, 2002;Shin et al, 2004), foi demonstrado que SRFS10 também pode induzir o processamento de RNAs na presença de um co-fator ainda não identificado (Feng et al, 2008). Ainda não se conhece a quinase capaz de fosforilar SRSF10, e a proteína parece ser induzida a desfosforilação na presença de andrógenos (testosterona) (Xiao et al, 2011).…”

“…De fato, foi demonstrado que essa proteína interfere no reconhecimento do sítio de splicing 5' por U1 snRNP presente em SNRNP70 (Shin et al, 2004).…”