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

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:iScience 2021-10, Vol.24 (10), p.103097, Article 103097
Hauptverfasser: Zhang, Xiaoli, Wang, Ze, Xu, Qing, Chen, Yuhan, Liu, Wen, Zhong, Tong, Li, Hongchang, Quan, Chengshi, Zhang, Lingqiang, Cui, Chun-Ping
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. [Display omitted] •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 Srsf5 Molecular physiology; Molecular biology; Molecular mechanism of gene regulation; Transcriptomics
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2021.103097