Journal
JOURNAL OF CELL BIOLOGY
Volume 195, Issue 1, Pages 27-40Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201107093
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Funding
- Japan Science and Technology Agency [21249013]
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Uehara Memorial Foundation
- Naito Foundation
- Takeda Science Foundation
- Program for Improvement of Research Environment for Young Researchers from Special Coordination Funds for Promoting Science and Technology
- Grants-in-Aid for Scientific Research [21249013] Funding Source: KAKEN
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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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