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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 translatio...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991368/
https://www.ncbi.nlm.nih.gov/pubmed/26992231
http://dx.doi.org/10.18632/oncotarget.8087
Descripción
Sumario: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.