RBM27 regulates cardiac function and diseases by maintaining the alternative splicing of Tnnt2 transcript

Correct mRNA splicing is important for maintaining heart function, and dysregulation of this process can result in heart failure. However, the molecular mechanisms underlying this process, particularly the role of RNA-binding protein (RBP) in regulating mRNA splicing, remain largely unclear. We identified RBM27 as an important regulator of cardiac function and diseases. Abnormal RBM27 expression was associated with myocardial infarction-induced heart failure. Cardiomyocyte-specific overexpression of RBM27 ameliorated myocardial infarction-induced heart failure, whereas cardiomyocyte-specific deletion of Rbm27 led to dilated cardiomyopathy and heart failure due to exon11 skipping in Tnnt2 . TNNT2, but not TNNT2Δexon11, rescued heart failure in Rbm27 -CKO mice. The RNA recognition motif (RRM) of RBM27 was essential for maintaining cardiac function by ensuring normal alternative splicing of Tnnt2 . RBM27 bound directly to the exon 11 region of Tnnt2 mRNA. These findings demonstrate that RBM27 plays a critical role in heart function by maintaining the normal alternative splicing of Tnnt2 , highlighting its importance in maintaining heart health.