Article

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

Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10065, USA.
Cell (Impact Factor: 33.12). 05/2012; 149(7):1635-46. DOI: 10.1016/j.cell.2012.05.003
Source: PubMed

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.

2 Followers
 · 
130 Views
 · 
6 Downloads
  • Source
    • ". 由于缺乏有效检测手段,相关研究多局 限于非编码 tRNA 和 rRNA,或小部分编码转录片段 [1] , 且多数 RNA 甲基化功能未知. 随着高通量测序技术发展[5]及一些 RNA 甲基化功能的发现 [6] [7] [8] [9] [10] [11] ,人们开始关注 RNA 甲基化研究. 尤 "
    [Show abstract] [Hide abstract]
    ABSTRACT: With the rapid development of high-throughput sequencing technologies, the emerging of methylated RNA immunoprecipitation sequencing (MeRIP-seq) technology makes it possible to detect RNA epigenetic modifications in a large scale, which allows transcriptome-wide profiling of RNA methylation. Mining the patterns of global mRNA methylation from these MeRIP-seq data can help reveal the potential functional roles of these mRNA methylations in regulating gene expression, splicing, RNA editing and RNA stability, effectively guiding the therapeutic intervention of cancer. Here, the principle of MeRIP-seq sequencing was first introduced. Then, the recent progress of the processing and analysis of MeRIP-seq data were comprehensively discussed. In the end, the computational problems and challenges faced in the process of MeRIP-seq data processing were also summarized.
    Progress in Biochemistry and Biophysics 06/2015; · 0.29 Impact Factor
  • Source
    • "See also Figures S1J and S1K. immunoprecipitation sequencing (RIPseq ) as described elsewhere (Dominissini et al., 2012; Meyer et al., 2012; Experimental Procedures). For each experiment , libraries were built for multiple biological replicates and concordant peaks for each experiment were used for subsequent bioinformatics analyses. "
    [Show abstract] [Hide abstract]
    ABSTRACT: N6-methyl-adenosine (m(6)A) is the most abundant modification on messenger RNAs and is linked to human diseases, but its functions in mammalian development are poorly understood. Here we reveal the evolutionary conservation and function of m(6)A by mapping the m(6)A methylome in mouse and human embryonic stem cells. Thousands of messenger and long noncoding RNAs show conserved m(6)A modification, including transcripts encoding core pluripotency transcription factors. m(6)A is enriched over 30 untranslated regions at defined sequence motifs and marks unstable transcripts, including transcripts turned over upon differentiation. Genetic inactivation or depletion of mouse and human Mettl3, one of the m(6)A methylases, led to m(6)A erasure on select target genes, prolonged Nanog expression upon differentiation, and impaired ESC exit from self-renewal toward differentiation into several lineages in vitro and in vivo. Thus, m(6)A is a mark of transcriptome flexibility required for stem cells to differentiate to specific lineages.
    Cell Stem Cell 12/2014; 15(6):707-719. DOI:10.1016/j.stem.2014.09.019 · 22.15 Impact Factor
  • Source
    • "During conjugation, both long, noncoding RNAs and 27 nt piRNAs are produced from the parental MAC and transported to the developing MAC, providing essential information about which sequences to retain and their rearrangement order (Fang et al., 2012; Nowacki et al., 2008). RNA adenosine methylation is a widespread and dynamically regulated posttranscriptional RNA modification (Meyer et al., 2012). It might function in Oxytricha to regulate noncoding RNAs or to mark specific sites or sequences on noncoding RNAs that guide genome rearrangement during development. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Programmed DNA rearrangements in the single-celled eukaryote Oxytricha trifallax completely rewire its germline into a somatic nucleus during development. This elaborate, RNA-mediated pathway eliminates noncoding DNA sequences that interrupt gene loci and reorganizes the remaining fragments by inversions and permutations to produce functional genes. Here, we report the Oxytricha germline genome and compare it to the somatic genome to present a global view of its massive scale of genome rearrangements. The remarkably encrypted genome architecture contains >3,500 scrambled genes, as well as >800 predicted germline-limited genes expressed, and some posttranslationally modified, during genome rearrangements. Gene segments for different somatic loci often interweave with each other. Single gene segments can contribute to multiple, distinct somatic loci. Terminal precursor segments from neighboring somatic loci map extremely close to each other, often overlapping. This genome assembly provides a draft of a scrambled genome and a powerful model for studies of genome rearrangement.
    Cell 08/2014; 158(5):1187-98. DOI:10.1016/j.cell.2014.07.034 · 33.12 Impact Factor
Show more

Preview

Download
6 Downloads
Available from