RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence
Copyright policy )RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence
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.
- National Institute of Health Pakistan
- Peking University China (People's Republic of)
- National Institute of Health (NIH/NICHD) United States
- National Institutes of Health United States
- National Institute on Aging United States
Src Homology 2 Domain-Containing, Transforming Protein 1, Blotting, Western, Methyltransferases, HCT116 Cells, Methylation, p38 Mitogen-Activated Protein Kinases, Oxidative Stress, Research Paper: Gerotarget (Focus on Aging), Gene Expression Regulation, CDC2 Protein Kinase, Human Umbilical Vein Endothelial Cells, Humans, RNA Interference, RNA, Messenger, Reactive Oxygen Species, Cells, Cultured, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p27
Src Homology 2 Domain-Containing, Transforming Protein 1, Blotting, Western, Methyltransferases, HCT116 Cells, Methylation, p38 Mitogen-Activated Protein Kinases, Oxidative Stress, Research Paper: Gerotarget (Focus on Aging), Gene Expression Regulation, CDC2 Protein Kinase, Human Umbilical Vein Endothelial Cells, Humans, RNA Interference, RNA, Messenger, Reactive Oxygen Species, Cells, Cultured, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p27
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