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PMID: 25389274 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nucleic acids research ·Vol. 42 ·No. 22 ·2014-12-16 ·Pages 13911-9

Theler D, Dominguez C, Blatter M, Boudet J, Allain FH

Abstract

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.

MeSH Terms
Adenosine/analogs & derivatives,chemistry Animals Binding Sites Guanine/chemistry Methylation Models, Molecular Nerve Tissue Proteins/chemistry,metabolism Nuclear Magnetic Resonance, Biomolecular Protein Binding Protein Structure, Tertiary RNA/chemistry,metabolism RNA-Binding Proteins/chemistry,metabolism Rats Serine-Arginine Splicing Factors
Chemicals
Nerve Tissue Proteins RNA-Binding Proteins Ythdc1 protein, rat Serine-Arginine Splicing Factors Guanine RNA N-methyladenosine Adenosine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Theler Dominik
Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland.
Dominguez Cyril
Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland.
Blatter Markus
Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland.
Boudet Julien
Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland.
Allain Frédéric H-T
Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland allain@mol.biol.ethz.ch.
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gku1116
Email
allain@mol.biol.ethz.ch
Published
2014-12-16
Epub
2014-00-11
Pages
13911-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC4267619
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gku1116 PMC Full Text View journal details
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