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

First Author  Ninomiya K Year  2011
Journal  J Cell Biol Volume  195
Issue  1 Pages  27-40
PubMed ID  21949414 Mgi Jnum  J:177723
Mgi Id  MGI:5295899 Doi  10.1083/jcb.201107093
Citation  Ninomiya K, et al. (2011) Stress-responsive maturation of Clk1/4 pre-mRNAs promotes phosphorylation of SR splicing factor. J Cell Biol 195(1):27-40
abstractText  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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