PIWI-Interacting RNA HAAPIR Regulates Cardiomyocyte Death After Myocardial Infarction by Promoting NAT10-Mediated ac 4 C Acetylation of Tfec mRNA.
Kai WangLu-Yu ZhouFang LiuLiang LinJie JuPeng-Chao TianCui-Yun LiuXin-Min LiXin-Zhe ChenTao WangFei WangShao-Cong WangJian ZhangYu-Hui ZhangJin-Wei TianKun WangPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2022)
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 4 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 4 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 4 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.
Keyphrases
- cell cycle arrest
- endoplasmic reticulum stress
- cell death
- oxidative stress
- high glucose
- heart failure
- transcription factor
- angiotensin ii
- binding protein
- endothelial cells
- left ventricular
- poor prognosis
- atrial fibrillation
- protein kinase
- histone deacetylase
- gene expression
- metabolic syndrome
- dna methylation
- climate change
- high fat diet induced
- nucleic acid