Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

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

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Oxidative demethylation of m6A in nucleic acids by FTO.
Figure 2: FTO regulates m6A content in mRNA in an FTO activity–dependent manner.
Figure 3: Indirect immunofluorescence analysis of endogenous FTO shows FTO partially colocalizes with nuclear speckles.

Similar content being viewed by others

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.

References

  1. Scott, L.J. et al. Science 316, 1341–1345 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Frayling, T.M. et al. Science 316, 889–894 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dina, C. et al. Nat. Genet. 39, 724–726 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Thorleifsson, G. et al. Nat. Genet. 41, 18–24 (2009).

    Article  CAS  PubMed  Google Scholar 

  5. Fischer, J. et al. Nature 458, 894–898 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. Church, C. et al. Nat. Genet. 42, 1086–1092 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gerken, T. et al. Science 318, 1469–1472 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kurowski, M.A., Bhagwat, A.S., Papaj, G. & Bujnicki, J.M. BMC Genomics 4, 48 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Westbye, M.P. et al. J. Biol. Chem. 283, 25046–25056 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Aas, P.A. et al. Nature 421, 859–863 (2003).

    Article  CAS  PubMed  Google Scholar 

  11. Fu, Y. et al. Angew. Chem. Int. Edn Engl. 49, 8885–8888 (2010).

    Article  CAS  Google Scholar 

  12. van den Born, E. et al. Nat. Commun. 2, 172 (2011).

    Article  PubMed  Google Scholar 

  13. Jia, G. et al. FEBS Lett. 582, 3313–3319 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lee, D.H. et al. J. Biol. Chem. 280, 39448–39459 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Han, Z. et al. Nature 464, 1205–1209 (2010).

    Article  CAS  PubMed  Google Scholar 

  16. Wei, C.M., Gershowitz, A. & Moss, B. Cell 4, 379–386 (1975).

    Article  CAS  PubMed  Google Scholar 

  17. Narayan, P. & Rottman, F.M. Science 242, 1159–1162 (1988).

    Article  CAS  PubMed  Google Scholar 

  18. Horowitz, S., Horowitz, A., Nilsen, T.W., Munns, T.W. & Rottman, F.M. Proc. Natl. Acad. Sci. USA 81, 5667–5671 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Harper, J.E., Miceli, S.M., Roberts, R.J. & Manley, J.L. Nucleic Acids Res. 18, 5735–5741 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bokar, J.A., Shambaugh, M.E., Polayes, D., Matera, A.G. & Rottman, F.M. RNA 3, 1233–1247 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Xie, S.Q. et al. Mol. Biol. Cell 17, 1723–1733 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hall, L.L. et al. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 288, 664–675 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lawrence, J.B. & Clemson, C.M. J. Cell Biol. 182, 1035–1038 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lamond, A.I. & Spector, D.L. Nat. Rev. Mol. Cell Biol. 4, 605–612 (2003).

    Article  CAS  PubMed  Google Scholar 

  25. He, C. Nat. Chem. Biol. 6, 863–865 (2010).

    Article  CAS  PubMed  Google Scholar 

Download references

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

Authors and Affiliations

Authors

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.

Corresponding author

Correspondence to Chuan He.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Methods and Supplementary Results (PDF 21210 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jia, G., Fu, Y., Zhao, X. et al. N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 7, 885–887 (2011). https://doi.org/10.1038/nchembio.687

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing