Solution structure of the YTH domain in complex with N6-methyladenosine RNA: a reader of methylated RNA

Nucleic Acids Res. 2014 Dec 16;42(22):13911-9. doi: 10.1093/nar/gku1116. Epub 2014 Nov 11.


N(6)A methylation is the most abundant RNA modification occurring within messenger RNA. Impairment of methylase or demethylase functions are associated with severe phenotypes and diseases in several organisms. Beside writer and eraser enzymes of this dynamic RNA epigenetic modification, reader proteins that recognize this modification are involved in numerous cellular processes. Although the precise characterization of these reader proteins remains unknown, preliminary data showed that most potential reader proteins contained a conserved YT521-B homology (YTH) domain. Here we define the YTH domain of rat YT521-B as a N(6)-methylated adenosine reader domain and report its solution structure in complex with a N(6)-methylated RNA. The structure reveals a binding preference for NGANNN RNA hexamer and a deep hydrophobic cleft for m(6)A recognition. These findings establish a molecular function for YTH domains as m(6)A reader domains and should guide further studies into the biological functions of YTH-containing proteins in m(6)A recognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Animals
  • Binding Sites
  • Guanine / chemistry
  • Methylation
  • Models, Molecular
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA / chemistry*
  • RNA / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism
  • Rats
  • Serine-Arginine Splicing Factors


  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Ythdc1 protein, rat
  • Serine-Arginine Splicing Factors
  • Guanine
  • RNA
  • N-methyladenosine
  • Adenosine