2. Academic Validation
  3. Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium

Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium

  • iScience. 2021 Sep 10;24(10):103097. doi: 10.1016/j.isci.2021.103097.
Xiaoli Zhang 1 2,  Ze Wang 2,  Qing Xu 3,  Yuhan Chen 2,  Wen Liu 2,  Tong Zhong 2,  Hongchang Li 2,  Chengshi Quan 1,  Lingqiang Zhang 2,  Chun-Ping Cui 2
Affiliations

Affiliations

  • 1 The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun, Jilin 130021, China.
  • 2 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 27 Taiping Road, Beijing 100850, China.
  • 3 Core Facilities Centre, Capital Medical University, Beijing 100069, China.
PMID: 34622152 DOI: 10.1016/j.isci.2021.103097
Abstract

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.

Keywords

Molecular biology; Molecular mechanism of gene regulation; Molecular physiology; Transcriptomics.

Figures
Products