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

被引:123
作者
Ninomiya, Kensuke [1 ]
Kataoka, Naoyuki [1 ]
Hagiwara, Masatoshi [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Anat & Dev Biol, Sakyo Ku, Kyoto 6068501, Japan
基金
日本科学技术振兴机构;
关键词
HEAT-SHOCK PROTEINS; INTRANUCLEAR DISTRIBUTION; CELL-CYCLE; RS DOMAIN; IN-VIVO; KINASE; SERINE; CLONING; FAMILY; RICH;
D O I
10.1083/jcb.201107093
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:27 / 40
页数:14
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