title: Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain.
abstract: N(6)-methyladenosine (m(6)A) 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 m(6)A-containing RNA. Our structural studies, together with transcriptome-wide identification of YTHDC1-binding sites and biochemical experiments, not only reveal the specific mode of m(6)A-YTH binding but also explain the preferential recognition of the GG(m(6)A)C sequences by YTHDC1.
authors.affiliation: 1] Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada. [2]. chaor.xu@utoronto.edu.
authors.forename: Chao
authors.identifier: 0000000304447080
authors.initials: C
authors.lastname: Xu
authors.affiliation: 1] Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA. [2] Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA. [3].
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1] Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada. [2].
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: 1] Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA. [2] Medical Scientist Training Program and Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Roundtree
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tempel
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1] Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA. [2] Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Zhike
authors.initials: Z
authors.lastname: Lu
authors.affiliation: 1] Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA. [2] Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.affiliation: 1] Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada. [2] Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Min
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C490769:YTHDC1 protein, human; D012313:RNA; C010223:N-methyladenosine; D000241:Adenosine