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.
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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.
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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).
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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.
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Supplementary Results, Supplementary Tables 1 and 2 and Supplementary Figures 1–12. (PDF 2897 kb)
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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
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DOI: https://doi.org/10.1038/nchembio.1654
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