Open AccessPIWI‐Interacting RNA HAAPIR Regulates Cardiomyocyte Death After Myocardial Infarction by Promoting NAT10‐Mediated ac 4 C Acetylation of Tfec mRNA
Author(s) -
Wang Kai,
Zhou LuYu,
Liu Fang,
Lin Liang,
Ju Jie,
Tian PengChao,
Liu CuiYun,
Li XinMin,
Chen XinZhe,
Wang Tao,
Wang Fei,
Wang ShaoCong,
Zhang Jian,
Zhang YuHui,
Tian JinWei,
Wang Kun
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202106058
Subject(s) - piwi interacting rna , acetylation , apoptosis , biology , messenger rna , transcription factor , transcription (linguistics) , downregulation and upregulation , microbiology and biotechnology , cancer research , rna , mitochondrion , rna interference , gene , biochemistry , linguistics , philosophy
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.