title: Methylation by NSun2 represses the levels and function of microRNA 125b.
abstract: Methylation is a prevalent posttranscriptional modification of RNAs. However, whether mammalian microRNAs are methylated is unknown. Here, we show that the tRNA methyltransferase NSun2 methylates primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vivo. Methylation by NSun2 inhibits the processing of pri-miR-125b2 into pre-miR-125b2, decreases the cleavage of pre-miR-125b2 into miR-125, and attenuates the recruitment of RISC by miR-125, thereby repressing the function of miR-125b in silencing gene expression. Our results highlight the impact of miR-125b function via methylation by NSun2.
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Junyue
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Han
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Zhuojun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Biological Chemistry, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Yali
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China wwg@bjmu.edu.cn.
authors.forename: Wengong
authors.initials: W
authors.lastname: Wang
mesh_terms: D002268:Carboxypeptidases / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008780:Methyltransferases / Q000235:genetics*; D035683:MicroRNAs / Q000378:metabolism*; D018384:Oxidative Stress; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D008780:Methyltransferases; C515610:NSUN2 protein, human; D002268:Carboxypeptidases; C436327:SCPEP1 protein, human