FTO-dependent demethylation of N6-methyladenosine regulates mRNA   splicing and is required for adipogenesis

doi:10.1038/cr.2014.151

CORC > 北京大学 > 化学与分子工程学院

	FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis
	Zhao, Xu ; Yang, Ying ; Sun, Bao-Fa ; Shi, Yue ; Yang, Xin ; Xiao, Wen ; Hao, Ya-Juan ; Ping, Xiao-Li ; Chen, Yu-Sheng ; Wang, Wen-Jia ; Jin, Kang-Xuan ; Wang, Xing ; Huang, Chun-Min ; Fu, Yu ; Ge, Xiao-Meng ; Song, Shu-Hui ; Jeong, Hyun Seok ; Yanagisawa, Hiroyuki ; Niu, Yamei ; Jia, Gui-Fang ; Wu, Wei ; Tong, Wei-Min ; Okamoto, Akimitsu ; He, Chuan ; Danielsen, Jannie M. Rendtlew ; Wang, Xiu-Jie ; Yang, Yun-Gui
刊名	细胞研究英文版
	2014
关键词	N6-methyladenosine (m(6)A) METTL3 FTO mRNA splicing adipogenesis OBESITY-ASSOCIATED FTO GENE-EXPRESSION HNRNP PROTEINS NUCLEAR-RNA REVEALS METHYLATION MOUSE SEQ M(6)A DIFFERENTIATION
DOI	10.1038/cr.2014.151
英文摘要	The role of Fat Mass and Obesity-associated protein (FTO) and its substrate N6-methyladenosine (m(6)A) in mRNA processing and adipogenesis remains largely unknown. We show that FTO expression and m(6)A levels are inversely correlated during adipogenesis. FTO depletion blocks differentiation and only catalytically active FTO restores adipogenesis. Transcriptome analyses in combination with m(6)A-seq revealed that gene expression and mRNA splicing of grouped genes are regulated by FTO. M(6)A is enriched in exonic regions flanking 5'- and 3'-splice sites, spatially overlapping with mRNA splicing regulatory serine/arginine-rich (SR) protein exonic splicing enhancer binding regions. Enhanced levels of m(6)A in response to FTO depletion promotes the RNA binding ability of SRSF2 protein, leading to increased inclusion of target exons. FTO controls exonic splicing of adipogenic regulatory factor RUNX1T1 by regulating m(6)A levels around splice sites and thereby modulates differentiation. These findings provide compelling evidence that FTO-dependent m(6)A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis.; Cell Biology; SCI(E); PubMed; 中国科技核心期刊(ISTIC); 中国科学引文数据库(CSCD); 0; ARTICLE; ygyang@big.ac.cn; 12; 1403-1419; 24
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/188516]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Zhao, Xu,Yang, Ying,Sun, Bao-Fa,et al. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis[J]. 细胞研究英文版,2014.
APA	Zhao, Xu.,Yang, Ying.,Sun, Bao-Fa.,Shi, Yue.,Yang, Xin.,...&Yang, Yun-Gui.(2014).FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis.细胞研究英文版.
MLA	Zhao, Xu,et al."FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis".细胞研究英文版 (2014).