title: NSUN2-Mediated m5C Methylation and METTL3/METTL14-Mediated m6A Methylation Cooperatively Enhance p21 Translation.
abstract: N6-methyladenosine (m6A) and m5C methylation are two major types of RNA methylation, but the impact of joint modifications on the same mRNA is unknown. Here, we show that in p21 3'UTR, NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Interestingly, methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2-mediated m5C and METTL3/METTL14-mediated m6A methylation synergistically enhance p21 expression at the translational level, leading to elevated expression of p21 in oxidative stress-induced cellular senescence. Our findings on p21 mRNA methylation and expression reveal that joint m6A and m5C modification of the same RNA may influence each other, coordinately affecting protein expression patterns. J. Cell. Biochem. 118: 2587-2598, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, P. R. China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, P. R. China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Biological Chemistry, University of Michigan, MSI 5215A, 1301 Catherine Street, Ann Arbor, Michigan, 48105.
authors.forename: Yali
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd., Baltimore, Maryland, 21224.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, P. R. China.
authors.forename: Wengong
authors.identifier: 0000-0002-1720-809X
authors.initials: W
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000241:Adenosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D016922:Cellular Senescence / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D014176:Protein Biosynthesis
chemical_list: D020413:3' Untranslated Regions; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C010223:N-methyladenosine; C587355:METTL14 protein, human; D008780:Methyltransferases; C515610:NSUN2 protein, human; C468275:METTL3 protein, human; D000241:Adenosine
keywords: METTL14; METTL3; NSUN2; TRANSLATIONAL REGULATION; p21 mRNA METHYLATION