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However, their functions and molecular mechanisms during myocardial infarction remain unknown. Here, a heart\u2010apoptosis\u2010associated piRNA (HAAPIR), which regulates cardiomyocyte apoptosis by targeting <jats:italic>N<\/jats:italic>\u2010acetyltransferase 10 (NAT10)\u2010mediated N4\u2010acetylcytidine (ac<jats:sup>4<\/jats:sup>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<jats:sup>4<\/jats:sup>C acetylation of Tfec mRNA transcript, which increases Tfec expression. TFEC can further upregulate the transcription of BCL2\u2010interacting killer (Bik), a pro\u2010apoptotic factor, which results in the accumulation of Bik and progression of cardiomyocyte apoptosis. The findings reveal that piRNA\u2010mediated ac<jats:sup>4<\/jats:sup>C acetylation mechanism is involved in the regulation of cardiomyocyte apoptosis. HAAPIR\u2010NAT10\u2010TFEC\u2010BIK signaling axis can be potential target for the reduction of myocardial injury caused by cardiomyocyte apoptosis in ischemia heart diseases.<\/jats:p>","DOI":"10.1002\/advs.202106058","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T07:51:03Z","timestamp":1644393063000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["PIWI\u2010Interacting RNA HAAPIR Regulates Cardiomyocyte Death After Myocardial Infarction by Promoting NAT10\u2010Mediated ac<sup>4<\/sup>C Acetylation of Tfec mRNA"],"prefix":"10.1002","volume":"9","author":[{"given":"Kai","family":"Wang","sequence":"first","affiliation":[{"name":"Institute for Translational Medicine The Affiliated Hospital of Qingdao University College of Medicine Qingdao University  Qingdao 266021 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