RBM15 Protects From Myocardial Infarction by Stabilizing NAE1

Abstract

RNA-binding proteins play multiple roles in several biological processes. However, the roles of RBM15—an important RNA-binding protein and a significant regulator of RNA methylation—in cardiovascular diseases remain elusive. This study aimed to investigate the biological function of RBM15 and its fundamental mechanisms in myocardial infarction (MI). Methylated RNA immunoprecipitation sequencing was used to explore the N6-methyladenosine (m⁶A) difference between MI and normal tissues. Our findings showed the elevated level of m⁶A in MI, and its transcription profile in both MI and normal tissues. RBM15 was the main regulator and its overexpression attenuated apoptosis in cardiomyocytes and improved cardiac function in mice after MI. Then, we used one target NEDD8 activating enzyme E1 subunit and its inhibitor (MLN4924) to investigate the impact of RBM15 targets on cardiomyocytes. Finally, the enhanced m⁶A methylation in the presence of RBM15 overexpression led to the increased expression and stability of NEDD8 activating enzyme E1 subunit. Our findings suggest that the enhanced m⁶A level is a protective mechanism in MI, and RBM15 is significantly upregulated in MI and promotes cardiac function. This study showed that RBM15 affected MI by stabilizing its target on the cell apoptosis function, which might provide a new insight into MI therapy.