Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3' UTRs and Near Stop Codons

By Kate D. Meyer, Yogesh Saletore, Paul Zumbo, Olivier Elemento, Christopher E. Mason, Samie R. Jaffrey. Cell, 2012

3,764 citations recorded by the source corpus.

SUMMARY Methylation of the N6 position of adenosine (m6A) is a post-transcriptional modification of RNA whose prevalence and physiological relevance is poorly understood. The recent discovery that FTO, an obesity risk gene, encodes an m6A demethylase implicates m6A as an important regulator of physiological processes. Here we present a method for transcriptome-wide m6A localization, which combines m6A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-Seq). We use this method to identify mRNAs of 7,676 mammalian genes that contain m6A, indicating that m6A is a common base modification of mRNA. The m6A modification exhibits tissue-specific regulation and is markedly increased throughout brain development. We find that m6A sites are enriched near stop codons and in 3' UTRs, and we uncover an association between m6A 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4609505d5353b1ce54ace3d6e637a11bcc401934

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Citations in the corpus

m6A-dependent regulation of messenger RNA stability (2013, positive): “Coinciding with the previously reported pattern of m 6 A peaks 14,15 , YTHDF2 PAR-CLIP peaks showed enrichment near the stop codon and in long exons (Extended Data Fig.”
A novel algorithm for calling mRNA m6A peaks by modeling biological variances in MeRIP-seq data (2016, background): “Recent surge of interest comes mainly as a result of two groundbreaking studies (Dominissini et al. , 2012; Meyer et al. , 2012) that show high abundancy of m 6 A in > 25% of transcripts in human and mouse cells.”
METTL3 promotes translation in human cancer cells (2016, background): “…and a metagene analysis revealed that m6A peaks were predominantly localized near stop codons, with a subset of m6A peaks located in the 50 UTR and internal exons (Figures 1A and 1B) (Dominissini et al., 2012; Meyer et al., 2012, 2015; Schwartz et al., 2014; Wang et al., 2014c; Zhou et al., 2015).”
FMRP Modulates Neural Differentiation through m6A-Dependent mRNA Nuclear Export (2019, neutral): “RNA methylation on N 6 -adenosine is emerging as a vital mechanism regulating RNA metabolism and function (Dominissini et al., 2012; Meyer et al., 2012; Peer et al., 2017).”
Rethinking m6A Readers, Writers, and Erasers (2017, methodology): “Interest in m6A was revived in 2012, when our group and the Rechavi group described MeRIP-Seq, a next-generation sequencing method to map m6A throughout the transcriptome (Dominissini et al. 2012, Meyer et al. 2012).”
Gene2vec: gene subsequence embedding for prediction of mammalian N6-methyladenosine sites from mRNA (2018, methodology): “Furthermore, high-throughput analysis of m 6 A, for instance, using the RNA immunoprecipitation biotechnologies MeRIP-seq and m6A-seq (Dominissini et al. 2012; Meyer et al. 2012), has provided insights into the functions and topological patterns of m 6 A mRNA modification.”
RNA modifications detection by comparative Nanopore direct RNA sequencing (2019, methodology): “Nanocompore includes several unique features: (1) robust signal realignment based on Nanopolish, (2) modelling of the biological variability, (3) ability to run multiple statistical tests, (4) prediction of RNA modifications using both signal intensity and duration (dwell time), and (5) availability”
m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells (2017, methodology): “Although m(6)A is most abundant in the brain (Meyer et al., 2012), no study on the role of m(6)A modification in either brain development or brain disorders has been reported previously, although recent studies have demonstrated a role form(6)A inDrosophila neuronal function (Haussmann et al.”