METTL3-dependent N <sup>6</sup> -methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium
Chian‐Shiu Chien, Julie Yi-Shuan Li, Yueh Chien, Mong‐Lien Wang, Aliaksandr A. Yarmishyn, Ping‐Hsing Tsai, Chi‐Chang Juan, Phu Hung Nguyen, Hao‐Min Cheng, Teh‐Ia Huo, Shih-Hwa Chiou, Shu Chien
Abstract
Significance Using in vitro and in vivo approaches, this report demonstrated the increased METTL3 expression and m 6 A hypermethylation in response to disturbed flow and oscillatory shear stress. METTL3 hypermethylates m 6 A sites at various downstream targets, up-regulates NLRP1 and down-regulates KLF4, and elicits atherogenic responses. Collectively, METTL3 and m 6 A hypermethylation epigenetically regulates the atherogenic gene expression and phenotypes in the initiation of atherosclerosis. Our data may enlighten the field of RNA epigenetics in the pathogenic mechanisms of heart diseases.