Stress-responsive maturation of Clk1/4 pre-mRNAs promotes phosphorylation of SR splicing factor.

Stress-responsive maturation of Clk1/4 pre-mRNAs promotes phosphorylation of SR splicing factor.
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DOI:
10.1083/jcb.201107093
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发表时间:
2011-10-03
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Hagiwara M
Hagiwara M
中科院分区:
其他
文献类型:
--
作者:
Ninomiya K;Kataoka N;Hagiwara M

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部分剪接的Clk1/4 pre- mrna核池在应激反应中成熟并诱导SR蛋白磷酸化和活化。人们一直认为,在基因表达过程中,前信使核糖核酸(RNAs; pre-mRNAs)是共转录剪接的。然而,在本文中,我们报道了Clk1/4 mrna的剪接在组织和培养细胞中悬浮,并且保留特定内含子的中间形式在细胞核中大量聚集。cdc2样激酶特异性抑制剂TG003通过促进内含子保留rna的剪接增加了Clk1/4成熟mrna的水平。在胁迫条件下,SR剪接因子的去磷酸化抑制了一般pre- mrna的剪接,但暴露于诸如热休克和渗透胁迫等胁迫下,促进了Clk1/4 mrna的成熟。热休克后翻译的Clk1/4蛋白催化SR蛋白的再磷酸化,尤其是SRSF4和SRSF10。这些发现表明,应力响应剪接诱导的Clk1/4表达有助于维持SR蛋白的磷酸化状态。
A nuclear pool of partially spliced Clk1/4 pre-mRNAs matures in response to stress and induces SR protein phosphorylation and activation. It has been assumed that premessenger ribonucleic acids (RNAs; pre-mRNAs) are spliced cotranscriptionally in the process of gene expression. However, in this paper, we report that splicing of Clk1/4 mRNAs is suspended in tissues and cultured cells and that intermediate forms retaining specific introns are abundantly pooled in the nucleus. Administration of the Cdc2-like kinase–specific inhibitor TG003 increased the level of Clk1/4 mature mRNAs by promoting splicing of the intron-retaining RNAs. Under stress conditions, splicing of general pre-mRNAs was inhibited by dephosphorylation of SR splicing factors, but exposure to stresses, such as heat shock and osmotic stress, promoted the maturation of Clk1/4 mRNAs. Clk1/4 proteins translated after heat shock catalyzed rephosphorylation of SR proteins, especially SRSF4 and SRSF10. These findings suggest that Clk1/4 expression induced by stress-responsive splicing serves to maintain the phosphorylation state of SR proteins.
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