NSUN2

RNA cytosine C(5)-methyltransferase NSUN2 (EC 2.1.1.-) (Myc-induced SUN domain-containing protein) (Misu) (NOL1/NOP2/Sun domain family member 2) (Substrate of AIM1/Aurora kinase B) (mRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-) (tRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-) (EC 2.1.1.203) (tRNA methyltransferase 4 homolog) (hTrm4) [SAKI] [TRM4]

Publications

RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence.

PubMed

Full text

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.

MeSH Terms

• Blotting, Western
• CDC2 Protein Kinase
• Cells, Cultured
• Cellular Senescence
• Cyclin-Dependent Kinase Inhibitor p27
• Gene Expression Regulation
• HCT116 Cells
• Human Umbilical Vein Endothelial Cells
• Humans
• Methylation
• Methyltransferases
• Oxidative Stress
• RNA Interference
• RNA, Messenger
• Reactive Oxygen Species
• Src Homology 2 Domain-Containing, Transforming Protein 1
• p38 Mitogen-Activated Protein Kinases

Keywords

• Gerotarget
• HUVEC
• NSUN2
• SHC mRNA methylation
• premature senescence
• translational regulation