Loss of m 6 A Methyltransferase METTL5 Promotes Cardiac Hypertrophy Through Epitranscriptomic Control of SUZ12 Expression

Frontiers in Cardiovascular Medicine

article

Yanchuang Han¹  Tailai Du¹  Siyao Guo¹  Lu Wang¹  Gang Dai²  Tianxin Long¹  Ting Xu¹  Xiaodong Zhuang¹  Chen Liu¹  Shujuan Li¹  Dihua Zhang³  Xinxue Liao¹  Yugang Dong¹  Kathy O. Lui⁴  Xu Tan⁵  Shuibin Lin¹  Yili Chen¹  Zhan-Peng Huang¹ 

[1] Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University;NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University;Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University;Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital;School of Pharmaceutical Sciences, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Tsinghua-Peking Center for Life Sciences

关键词: cardiac hypertrophy;    METTL5;    RNA modification;    translational regulation;    SUZ12;   

DOI  :  10.3389/fcvm.2022.852775

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

Enhancement of protein synthesis from mRNA translation is one of the key steps supporting cardiomyocyte hypertrophy during cardiac remodeling. The methyltransferase-like5 (METTL5), which catalyzes m 6 A modification of 18S rRNA at position A 1832 , has been shown to regulate the efficiency of mRNA translation during the differentiation of ES cells and the growth of cancer cells. It remains unknown whether and how METTL5 regulates cardiac hypertrophy. In this study, we have generated a mouse model, METTL5-cKO, with cardiac-specific depletion of METTL5 in vivo . Loss function of METTL5 promotes pressure overload-induced cardiomyocyte hypertrophy and adverse remodeling. The regulatory function of METTL5 in hypertrophic growth of cardiomyocytes was further confirmed with both gain- and loss-of-function approaches in primary cardiomyocytes. Mechanically, METTL5 can modulate the mRNA translation of SUZ12, a core component of PRC2 complex, and further regulate the transcriptomic shift during cardiac hypertrophy. Altogether, our study may uncover an important translational regulator of cardiac hypertrophy through m6A modification.

【 授权许可】

CC BY