title: Stress-responsive maturation of Clk1/4 pre-mRNAs promotes phosphorylation of SR splicing factor.
abstract: 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.
authors.affiliation: Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ninomiya
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kataoka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hagiwara
mesh_terms: D000818:Animals; D018869:Heat-Shock Response / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009997:Osmotic Pressure / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C487497:TG 003; D013844:Thiazoles; C066780:Clk dual-specificity kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases