title: Overexpression of Dyrk1A regulates cardiac troponin T splicing in cells and mice.
abstract: The human heart expresses four isoforms of cardiac troponin T (cTnT) through alternative splicing of exons 4 and 5 of the cTnT gene. Alternative splicing of cTnT exon 5 is developmentally regulated. cTnT isoforms containing exon 5 are expressed in the fetal and neonatal heart but not in the mature heart. SRp55 is an essential splicing factor involved in cTnT exon 5 splicing and it is phosphorylated by Dyrk1A (dual specificity tyrosine phosphorylation regulated kinase 1A). In the present study, we found Dyrk1A interacted with SRp55 and enhanced its promotion of cTnT exon 5 inclusion. The shift from cTnT exon 5 inclusion to exclusion during development was delayed in the heart of Ts65Dn mice due to Dyrk1A overexpression. These results provide new insight into the role of Dyrk1A in the neonatal cardiac development.
authors.affiliation: Department of Intensive Care Unit, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, PR China.
authors.forename: Shu
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Biochemistry, Medical School, Nantong University, Nantong, Jiangsu, 226001, PR China; Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China. Electronic address: yinxiaomin@126.com.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yin
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D005091:Exons; D057809:HEK293 Cells; D006321:Heart / Q000254:growth & development; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors / Q000502:physiology; D020107:Troponin T / Q000235:genetics* / Q000378:metabolism; D000097603:Dyrk Kinases
chemical_list: D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000068103:Serine-Arginine Splicing Factors; D020107:Troponin T; D000097603:Dyrk Kinases; C489470:SRSF6 protein, human
keywords: Alternative splicing; Cardiac troponin T; Dyrk1A; Exon 5