Abstract

Background: Aberrant alternative splicing (AS) events, triggered by the alterations in serine/arginine splicing factor 1 (SRSF1), a member of the SR protein family, have been implicated in various pathological processes. However, the function and mechanism of SRSF1 in cardiovascular diseases remain unclear.

Results: In this study, we found that the expression of SRSF1 was significantly down-regulated in the hearts of mice with acute myocardial infarction (AMI) and H9C2 cells exposed to H₂O₂. Moreover, in vivo experiments utilizing adeno-associated virus serotype 9-mediated SRSF1 overexpression improved cardiac function and reduced infarct size in AMI mice. Mechanistically, we employed RNA-seq assay to identify AS aberrations associated with altered SRSF1 level in cardiomyocytes, and found that SRSF1 regulates the splice switching of Bcl2L12. Further study showed that silencing SRSF1 inhibits the inclusion of exon7 in Bcl2L12. Importantly, the truncated Bcl2L12 lacked the necessary structural elements and failed to interact with p53, thus compromising its ability to suppress apoptosis.

Conclusions: Our study unraveled the role of SRSF1 as a splicing factor involved in the regulation of Bcl2L12 splice switching, thereby exerting an anti-apoptotic effect through the p53 pathway, which provides new insights into potential approaches targeting cardiomyocyte apoptosis in cardiovascular diseases.