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:

Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain

A Corrigendum to this article was published on 17 September 2015

This article has been updated

Abstract

N6-methyladenosine (m6A) is the most abundant internal modification of nearly all eukaryotic mRNAs and has recently been reported to be recognized by the YTH domain family proteins. Here we present the crystal structures of the YTH domain of YTHDC1, a member of the YTH domain family, and its complex with an m6A-containing RNA. Our structural studies, together with transcriptome-wide identification of YTHDC1-binding sites and biochemical experiments, not only reveal the specific mode of m6A-YTH binding but also explain the preferential recognition of the GG(m6A)C sequences by YTHDC1.

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: YTHDC1 is a nuclear m6A reader.
Figure 2: Structural basis of preferential recognition of the GG(m6A)C consensus motif by the YTH domain of YTHDC1.

Similar content being viewed by others

Accession codes

Primary accessions

Protein Data Bank

Referenced accessions

Protein Data Bank

Change history

  • 19 August 2015

    In the version of this Brief Communication initially published, the email address for corresponding author, Chao Xu, was incorrect. It should be listed as chaor.xu@utoronto.edu. This error has been corrected in the PDF and HTML versions of the article.

  • 11 November 2015

    In the version of this Brief Communication initially published, as well as in a corrected version of 19 August 2015, incorrect e-mail addresses were given for corresponding author Chao Xu. The correct address is chaor.xu@utoronto.ca. This error has been corrected in the PDF and HTML versions of the article.

References

  1. Tuck, M.T. Int. J. Biochem. 24, 379–386 (1992).

    Article  CAS  Google Scholar 

  2. Schwartz, S. et al. Cell 155, 1409–1421 (2013).

    Article  CAS  Google Scholar 

  3. Wei, C.M. & Moss, B. Biochemistry 16, 1672–1676 (1977).

    Article  CAS  Google Scholar 

  4. Zhong, S. et al. Plant Cell 20, 1278–1288 (2008).

    Article  CAS  Google Scholar 

  5. Bokar, J.A. Fine-tuning of RNA functions by modification and editing. Vol. 12 (ed. Grosjean, H.) 141–177 (Springer-Verlag, Berlin Heidelberg, 2005).

  6. Hongay, C.F. & Orr-Weaver, T.L. Proc. Natl. Acad. Sci. USA 108, 14855–14860 (2011).

    Article  CAS  Google Scholar 

  7. Dominissini, D. et al. Nature 485, 201–206 (2012).

    Article  CAS  Google Scholar 

  8. Meyer, K.D. et al. Cell 149, 1635–1646 (2012).

    Article  CAS  Google Scholar 

  9. Fu, Y., Dominissini, D., Rechavi, G. & He, C. Nat. Rev. Genet. 15, 293–306 (2014).

    Article  CAS  Google Scholar 

  10. Jia, G. et al. Nat. Chem. Biol. 7, 885–887 (2011).

    Article  CAS  Google Scholar 

  11. Zheng, G. et al. Mol. Cell 49, 18–29 (2013).

    Article  CAS  Google Scholar 

  12. Liu, J. et al. Nat. Chem. Biol. 10, 93–95 (2014).

    Article  CAS  Google Scholar 

  13. Wang, Y. et al. Nat. Cell Biol. 16, 191–198 (2014).

    Article  CAS  Google Scholar 

  14. Wang, X. et al. Nature 505, 117–120 (2014).

    Article  Google Scholar 

  15. Zhang, Z. et al. J. Biol. Chem. 285, 14701–14710 (2010).

    Article  CAS  Google Scholar 

  16. Nayler, O., Hartmann, A.M. & Stamm, S. J. Cell Biol. 150, 949–962 (2000).

    Article  CAS  Google Scholar 

  17. Zhang, B. et al. Int. J. Gynecol. Cancer 20, 492–499 (2010).

    Article  Google Scholar 

  18. Hirschfeld, M. et al. Mol. Carcinog. 10.1002/mc.22045 (13 June 2013).

  19. Hafner, M. et al. Cell 141, 129–141 (2010).

    Article  CAS  Google Scholar 

  20. Jacobs, S.A. & Khorasanizadeh, S. Science 295, 2080–2083 (2002).

    Article  CAS  Google Scholar 

  21. Wang, G.G. et al. Nature 459, 847–851 (2009).

    Article  CAS  Google Scholar 

  22. Zou, X., Ma, W., Solov'yov, I.A., Chipot, C. & Schulten, K. Nucleic Acids Res. 40, 2747–2758 (2012).

    Article  CAS  Google Scholar 

  23. Marcotrigiano, J., Gingras, A.C., Sonenberg, N. & Burley, S.K. Cell 89, 951–961 (1997).

    Article  CAS  Google Scholar 

  24. Kabsch, W. Acta Crystallogr. D Biol. Crystallogr. 66, 125–132 (2010).

    Article  CAS  Google Scholar 

  25. Evans, P.R. & Murshudov, G.N. Acta Crystallogr. D Biol. Crystallogr. 69, 1204–1214 (2013).

    Article  CAS  Google Scholar 

  26. McCoy, A.J. et al. J. Appl. Crystallogr. 40, 658–674 (2007).

    Article  CAS  Google Scholar 

  27. Lebedev, A.A. et al. Acta Crystallogr. D Biol. Crystallogr. 68, 431–440 (2012).

    Article  CAS  Google Scholar 

  28. Murshudov, G.N. et al. Acta Crystallogr. D Biol. Crystallogr. 67, 355–367 (2011).

    Article  CAS  Google Scholar 

  29. Chen, V.B. et al. Acta Crystallogr. D Biol. Crystallogr. 66, 12–21 (2010).

    Article  CAS  Google Scholar 

  30. Hafner, M. et al. J. Vis. Exp. 2 10.3791/2034 (2010).

  31. Pearson, W.R., Wood, T., Zhang, Z. & Miller, W. Genomics 46, 24–36 (1997).

    Article  CAS  Google Scholar 

  32. Trapnell, C., Pachter, L. & Salzberg, S.L. Bioinformatics 25, 1105–1111 (2009).

    Article  CAS  Google Scholar 

  33. Corcoran, D.L. et al. Genome Biol. 12, R79 (2011).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank J. Walker for assistance in structure determination. The SGC is a registered charity (number 1097737) that receives funds from AbbVie, Boehringer Ingelheim, the Canada Foundation for Innovation, the Canadian Institutes for Health Research, Genome Canada through the Ontario Genomics Institute (OGI-055), GlaxoSmithKline, Janssen, Lilly Canada, the Novartis Research Foundation, the Ontario Ministry of Economic Development and Innovation, Pfizer, Takeda and the Wellcome Trust (092809/Z/10/Z to J.M.). C.H. is supported by the Howard Hughes Medical Institute as an investigator. The Mass Spectrometry Facility of the University of Chicago is funded by the National Science Foundation (CHE-1048528).

Author information

Authors and Affiliations

Authors

Contributions

C.X. and J.M. conceived the project; C.X. performed the structural and binding experiments with assistance from K.L., W.T. and Y.L.; X.W. and I.A.R. conducted the PAR-CLIP experiment of YTHDC1; Z.L. and X.W. analyzed the PAR-CLIP data. C.X., X.W., C.H. and J.M. wrote the manuscript. All authors contributed to editing the manuscript. C.H. and J.M. supervised the project.

Corresponding authors

Correspondence to Chao Xu, Chuan He or Jinrong Min.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Results, Supplementary Tables 1 and 2 and Supplementary Figures 1–12. (PDF 2897 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, C., Wang, X., Liu, K. et al. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat Chem Biol 10, 927–929 (2014). https://doi.org/10.1038/nchembio.1654

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.1654

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