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

Nat Chem Biol. 2014 Nov;10(11):927-9. doi: 10.1038/nchembio.1654. Epub 2014 Sep 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / metabolism
  • RNA / chemistry*
  • RNA / metabolism
  • RNA Splicing Factors
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism

Substances

  • Nerve Tissue Proteins
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • YTHDC1 protein, human
  • RNA
  • N-methyladenosine
  • Adenosine

Associated data

  • GEO/GSE58352
  • PDB/4R3H
  • PDB/4R3I