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

Nature Chemical Biology volume 7, pages 885887 (2011) | Download Citation

  • A Corrigendum to this article was published on 26 November 2012

This article has been updated

Abstract

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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Change history

  • 03 July 2012

    In the version of this article initially published, one of the institute affiliations of co–first author Xu Zhao and coauthors Ying Yang and Yun-Gui Yang was not included. The affiliations statement has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

This work is supported by the US National Institutes of Health (NIH) (GM071440 to C.H.), an NIH EUREKA award (GM088599 to C.H. and T.P.) and the Chinese Academy of Sciences (CAS) '100 Talents' Professor Program to Y.-G.Y. Q.D. is supported by the Chicago Biomedical Consortium (CBC). X.Z. and Y.Y. are supported by the Graduate Student Program of the Beijing Institute of Genomics at CAS. T.L. is supported by the CAS Senior Foreign Research Fellow Award (2009S2-1). We thank the CBC and University of Illinois at Chicago Research Resources Center Proteomics and Informatics Services Facility for performing the LC-MS/MS analysis, L.A. Godley for the suggestion and P. Jin for providing the pcDNA3-FTO plasmid. We thank S.F. Reichard for editing the manuscript.

Author information

Author notes

    • Guifang Jia
    • , Ye Fu
    •  & Xu Zhao

    These authors contributed equally to this work.

Affiliations

  1. Department of Chemistry, University of Chicago, Chicago, Illinois, USA.

    • Guifang Jia
    • , Ye Fu
    • , Qing Dai
    • , Guanqun Zheng
    •  & Chuan He
  2. 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
  3. Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.

    • Chengqi Yi
    •  & Tao Pan
  4. Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK.

    • Tomas Lindahl
  5. Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois, USA.

    • Tao Pan
    •  & Chuan He
  6. Graduate University of Chinese Academy of Sciences, Beijing, China.

    • Xu Zhao
    • , Ying Yang
    •  & Yun-Gui Yang

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Contributions

G.J., Y.F. and C.H. conceived the original idea. G.J., Y.F., X.Z., Y.-G.Y and C.H. designed the experiments with the help of T.P. Biochemistry assays and cellular analysis were performed by G.J., Y.F. and X.Z. with the help of G.Z., C.Y. and Y.Y.; Q.D. carried out the chemical synthesis; T.L. provided advice and the anti-FTO antibody; and G.J., Y.F., Y.-G.Y. and C.H. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Chuan He.

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DOI

https://doi.org/10.1038/nchembio.687

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