| First Author | Zhang X | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 10 | Pages | 103097 |
| PubMed ID | 34622152 | Mgi Jnum | J:311867 |
| Mgi Id | MGI:6780784 | Doi | 10.1016/j.isci.2021.103097 |
| Citation | Zhang X, et al. (2021) Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium. iScience 24(10):103097 |
| abstractText | The 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, Srsf5 knockout (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 in Srsf5 (-/-) 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 in Srsf5-deficient heart. These findings indicate that Srsf5-regulated alternative splicing plays a critical role during heart development. |
