RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence

Abstract

// Xiaoyu Cai 1,* , Yuanyuan Hu 1,* , Hao Tang 2 , Han Hu 1 , Lijun Pang 1 , Junyue Xing 1 , Zhenyun Liu 1 , Yuhong Luo 2 , Bin Jiang 1 , Te Liu 4 , Myriam Gorospe 3 , Chuan Chen 4 and Wengong Wang 1 1 Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, P. R. China 2 Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, P.R. China 3 Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA 4 Shanghai Geriatric Institute of Chinese Medicine, Shanghai, China * These authors have contributted equally to this work Correspondence to: Chuan Chen, email: // Wengong Wang, email: // Keywords : NSUN2, SHC mRNA methylation, translational regulation, HUVEC, premature senescence, Gerotarget Received : January 25, 2016 Accepted : February 23, 2016 Published : March 15, 2016 Abstract The tRNA methyltransferase NSUN2 delays replicative senescence by regulating the translation of CDK1 and CDKN1B mRNAs. However, whether NSUN2 influences premature cellular senescence remains untested. Here we show that NSUN2 methylates SHC mRNA in vitro and in cells, thereby enhancing the translation of the three SHC proteins, p66SHC, p52SHC, and p46SHC. Our results further show that the elevation of SHC expression by NSUN2-mediated mRNA methylation increased the levels of ROS, activated p38MAPK, thereby accelerating oxidative stress- and high-glucose-induced senescence of human vascular endothelial cells (HUVEC). Our findings highlight the critical impact of NSUN2-mediated mRNA methylation in promoting premature senescence.