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 |