title: Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons.
abstract: Methylation of the N(6) position of adenosine (m(6)A) is a posttranscriptional modification of RNA with poorly understood prevalence and physiological relevance. The recent discovery that FTO, an obesity risk gene, encodes an m(6)A demethylase implicates m(6)A as an important regulator of physiological processes. Here, we present a method for transcriptome-wide m(6)A localization, which combines m(6)A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-Seq). We use this method to identify mRNAs of 7,676 mammalian genes that contain m(6)A, indicating that m(6)A is a common base modification of mRNA. The m(6)A modification exhibits tissue-specific regulation and is markedly increased throughout brain development. We find that m(6)A sites are enriched near stop codons and in 3' UTRs, and we uncover an association between m(6)A residues and microRNA-binding sites within 3' UTRs. These findings provide a resource for identifying transcripts that are substrates for adenosine methylation and reveal insights into the epigenetic regulation of the mammalian transcriptome.
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Kate D
authors.initials: KD
authors.lastname: Meyer
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Saletore
authors.forename: Paul
authors.initials: P
authors.lastname: Zumbo
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Mason
authors.forename: Samie R
authors.initials: SR
authors.lastname: Jaffrey
mesh_terms: D020413:3' Untranslated Regions; D000241:Adenosine / Q000378:metabolism; D018388:Codon, Terminator; D008745:Methylation; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D018388:Codon, Terminator; D012333:RNA, Messenger; D022661:RNA, Untranslated; D000241:Adenosine