PIWI-Interacting RNA HAAPIR Regulates Cardiomyocyte Death After Myocardial Infarction by Promoting NAT10-Mediated ac C Acetylation of Tfec mRNA.

PIWI-interacting RNAs (piRNAs) are abundantly expressed in heart. However, their functions and molecular mechanisms during myocardial infarction remain unknown. Here, a heart-apoptosis-associated piRNA (HAAPIR), which regulates cardiomyocyte apoptosis by targeting N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac C) acetylation of transcription factor EC (Tfec) mRNA transcript, is identified. HAAPIR deletion attenuates ischemia/reperfusion induced myocardial infarction and ameliorate cardiac function compared to WT mice. Mechanistically, HAAPIR directly interacts with NAT10 and enhances ac C acetylation of Tfec mRNA transcript, which increases Tfec expression. TFEC can further upregulate the transcription of BCL2-interacting killer (Bik), a pro-apoptotic factor, which results in the accumulation of Bik and progression of cardiomyocyte apoptosis. The findings reveal that piRNA-mediated ac C acetylation mechanism is involved in the regulation of cardiomyocyte apoptosis. HAAPIR-NAT10-TFEC-BIK signaling axis can be potential target for the reduction of myocardial injury caused by cardiomyocyte apoptosis in ischemia heart diseases.