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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Scott, L.J. et al. Science 316, 1341–1345 (2007).
Frayling, T.M. et al. Science 316, 889–894 (2007).
Dina, C. et al. Nat. Genet. 39, 724–726 (2007).
Thorleifsson, G. et al. Nat. Genet. 41, 18–24 (2009).
Fischer, J. et al. Nature 458, 894–898 (2009).
Church, C. et al. Nat. Genet. 42, 1086–1092 (2010).
Gerken, T. et al. Science 318, 1469–1472 (2007).
Kurowski, M.A., Bhagwat, A.S., Papaj, G. & Bujnicki, J.M. BMC Genomics 4, 48 (2003).
Westbye, M.P. et al. J. Biol. Chem. 283, 25046–25056 (2008).
Aas, P.A. et al. Nature 421, 859–863 (2003).
Fu, Y. et al. Angew. Chem. Int. Edn Engl. 49, 8885–8888 (2010).
van den Born, E. et al. Nat. Commun. 2, 172 (2011).
Jia, G. et al. FEBS Lett. 582, 3313–3319 (2008).
Lee, D.H. et al. J. Biol. Chem. 280, 39448–39459 (2005).
Han, Z. et al. Nature 464, 1205–1209 (2010).
Wei, C.M., Gershowitz, A. & Moss, B. Cell 4, 379–386 (1975).
Narayan, P. & Rottman, F.M. Science 242, 1159–1162 (1988).
Horowitz, S., Horowitz, A., Nilsen, T.W., Munns, T.W. & Rottman, F.M. Proc. Natl. Acad. Sci. USA 81, 5667–5671 (1984).
Harper, J.E., Miceli, S.M., Roberts, R.J. & Manley, J.L. Nucleic Acids Res. 18, 5735–5741 (1990).
Bokar, J.A., Shambaugh, M.E., Polayes, D., Matera, A.G. & Rottman, F.M. RNA 3, 1233–1247 (1997).
Xie, S.Q. et al. Mol. Biol. Cell 17, 1723–1733 (2006).
Hall, L.L. et al. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 288, 664–675 (2006).
Lawrence, J.B. & Clemson, C.M. J. Cell Biol. 182, 1035–1038 (2008).
Lamond, A.I. & Spector, D.L. Nat. Rev. Mol. Cell Biol. 4, 605–612 (2003).
He, C. Nat. Chem. Biol. 6, 863–865 (2010).
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.
The authors declare no competing financial interests.
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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
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