SRp38 regulates alternative splicing and is required for Ca(2+) handling in the embryonic heart.

Document Type


Publication Date



Animals, Base-Sequence, Calcium, Carrier-Proteins, Cell-Cycle-Proteins, Cell-Separation, Chickens, Edema, Embryo-Loss, Embryo-Mammalian, Exons, Gene-Expression-Regulation-Developmental, Heart, Heart-Defects-Congenital, Liver, Mice, Molecular-Sequence-Data, Muscle-Proteins, Myocytes-Cardiac, Neoplasm-Proteins, Protein-Binding, RNA-Precursors, RNA-Binding-Proteins, Repressor-Proteins, Transfection

First Page


Last Page


JAX Source

Dev Cell 2009 Apr; 16(4):528-38.


SRp38 is an atypical SR protein splicing regulator. To define the functions of SRp38 in vivo, we generated SRp38 null mice. The majority of homozygous mutants survived only until E15.5 and displayed multiple cardiac defects. Evaluation of gene expression profiles in the SRp38(-/-) embryonic heart revealed a defect in processing of the pre-mRNA encoding cardiac triadin, a protein that functions in regulation of Ca(2+) release from the sarcoplasmic reticulum during excitation-contraction coupling. This defect resulted in significantly reduced levels of triadin, as well as those of the interacting protein calsequestrin 2. Purified SRp38 was shown to bind specifically to the regulated exon and to modulate triadin splicing in vitro. Extending these results, isolated SRp38(-/-) embryonic cardiomyocytes displayed defects in Ca(2+) handling compared with wild-type controls. Taken together, our results demonstrate that SRp38 regulates cardiac-specific alternative splicing of triadin pre-mRNA and, reflecting this, is essential for proper Ca(2+) handling during embryonic heart development.