N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO

Author: Guifang Jia, Ye Fu, Xu Zhao, Qing Dai, Guanqun Zheng, Ying Yang, Chengqi Yi, Tomas Lindahl, Tao Pan, Yun-Gui Yang & Chuan He
Affiliation:
Department of Chemistry, University of Chicago, Chicago, Illinois, USA. Guifang Jia, Ye Fu, Qing Dai, Guanqun Zheng & Chuan He Genome Structure and Stability Group, Disease Genomics and Individualized Medicine Laboratory, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. Xu Zhao, Ying Yang & Yun-Gui Yang Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA. Chengqi Yi & Tao Pan Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK. Tomas Lindahl Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois, USA. Tao Pan & Chuan He
Conference/Journal: nature chemical biology
Date published: 2011 Oct 16
Other: Special Notes: doi:10.1038/nchembio.687 , Word Count: 82


We report here that fat mass and obesity-associated protein (FTO) has efficient oxidative demethylation activity targeting the abundant N6-methyladenosine (m6A) residues in RNA in vitro. FTO knockdown with siRNA led to increased amounts of m6A in mRNA, whereas overexpression of FTO resulted in decreased amounts of m6A in human cells. We further show the partial colocalization of FTO with nuclear speckles, which supports the notion that m6A in nuclear RNA is a major physiological substrate of FTO.

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