期刊
ONCOTARGET
卷 7, 期 15, 页码 19099-19110出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8087
关键词
NSUN2; SHC mRNA methylation; translational regulation; HUVEC; premature senescence; Gerotarget
资金
- National Science Foundation of China [81373706, 81230008, 81420108016, 91339114]
- (111 project) from the Ministry of Education of People's Republic of China [B07001]
- NIA-IRP, NIH
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.
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