摘要：SummaryThe serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5 in tissue development and disease remains unknown. Here,Srsf5knockout (Srsf5−/−) mice were generated using CRISPR-Cas9. Mutant mice were perinatally lethal and exhibited cardiac dysfunction with noncompaction of the ventricular myocardium. The left ventricular internal diameter and volume were increased inSrsf5−/−mice during systole. Null mice had abnormal electrocardiogram patterns, indicative of a light atrioventricular block. Mechanistically, Srsf5 promoted the alternative splicing of Myom1 (myomesin-1), a protein that crosslinks myosin filaments to the sarcomeric M-line. The switch between embryonic and adult isoforms of Myom1 could not be completed inSrsf5-deficient heart. These findings indicate that Srsf5-regulated alternative splicing plays a critical role during heart development.Graphical abstractDisplay OmittedHighlights•Systemic loss of Srsf5 causes perinatal lethality in mice•Srsf5 deficiency leads to cardiac dysfunction•Alternative splicing of Myom1 in the heart around birth is regulated by Srsf5Molecular physiology; Molecular biology; Molecular mechanism of gene regulation; Transcriptomics
