title: RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Junyue
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Zhenyun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Shanghai, P.R. China.
authors.forename: Te
authors.initials: T
authors.lastname: Liu
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Shanghai, P.R. China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, P.R. China.
authors.forename: Wengong
authors.initials: W
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C528024:SHC1 protein, human; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008780:Methyltransferases; C515610:NSUN2 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Gerotarget; HUVEC; NSUN2; SHC mRNA methylation; premature senescence; translational regulation