Title RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence
Authors Cai, Xiaoyu
Hu, Yuanyuan
Tang, Hao
Hu, Han
Pang, Lijun
Xing, Junyue
Liu, Zhenyun
Luo, Yuhong
Jiang, Bin
Liu, Te
Gorospe, Myriam
Chen, Chuan
Wang, Wengong
Affiliation Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China.
Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China.
NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
Shanghai Geriatr Inst Chinese Med, Shanghai, Peoples R China.
Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China.
Chen, C (reprint author), Shanghai Geriatr Inst Chinese Med, Shanghai, Peoples R China.
Keywords NSUN2
SHC mRNA methylation
translational regulation
HUVEC
premature senescence
Gerotarget
DELAYS REPLICATIVE SENESCENCE
16S RIBOSOMAL-RNA
OXIDATIVE STRESS
ESCHERICHIA-COLI
SIGNALING PATHWAY
LONGEVITY GENE
MESSENGER-RNA
LIFE-SPAN
P66SHC
P66(SHC)
Issue Date 2016
Publisher ONCOTARGET
Citation ONCOTARGET.2016,7,(15),19099-19110.
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.
URI http://hdl.handle.net/20.500.11897/434452
ISSN 1949-2553
DOI 10.18632/oncotarget.8087
Indexed SCI(E)
PubMed
Appears in Collections: 医学部待认领

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