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Review
. 2016 Jun 17;352(6292):1408-12.
doi: 10.1126/science.aad8711.

Messenger RNA modifications: Form, distribution, and function

Wendy V Gilbert  1 , Tristan A Bell  2 , Cassandra Schaening  3
Affiliations
Review

Messenger RNA modifications: Form, distribution, and function

Wendy V Gilbert et al. Science. .

Abstract

RNA contains more than 100 distinct modifications that promote the functions of stable noncoding RNAs in translation and splicing. Recent technical advances have revealed widespread and sparse modification of messenger RNAs with N(6)-methyladenosine (m(6)A), 5-methylcytosine (m(5)C), and pseudouridine (Ψ). Here we discuss the rapidly evolving understanding of the location, regulation, and function of these dynamic mRNA marks, collectively termed the epitranscriptome. We highlight differences among modifications and between species that could instruct ongoing efforts to understand how specific mRNA target sites are selected and how their modification is regulated. Diverse molecular consequences of individual m(6)A modifications are beginning to be revealed, but the effects of m(5)C and Ψ remain largely unknown. Future work linking molecular effects to organismal phenotypes will broaden our understanding of mRNA modifications as cell and developmental regulators.

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Figures

Fig. 1
Fig. 1. Nucleotide modifications and detection strategies
For each modification, the chemical structure (left), detection strategy (right), and sample output of mapped sequencing reads (bottom) are shown. (A) For detection of m6A, antibodies are used to select methylated RNA fragments. A typical broad peak in read coverage overlaps an m6A site. nt, nucleotide. (B) Ψ are detected as CMC-dependent reverse transcriptase stops at the 3' end of the U site. (C) m5C is protected from conversion into U during bisulfite treatment, and putative sites are identified by their high rates of nonconversion. Each row represents one sequencing read, and filled squares indicate unconverted Cs. me, methylated site.
Fig. 2
Fig. 2. Diverse molecular functions of m6A, Ψ, and m5C in coding RNAs
Nascent RNA transcripts in eukaryotic cells are chemically modified (red dot) by m6A, Ψ, and m5C “writer” enzymes. In the nucleus, m6A, and potentially other modifications, alters processing of pre-mRNA and pri-miRNA, through both direct recognition and induced changes in RNA secondary structure (,,). After export to the cytoplasm, which is enhanced by m6A (), mRNA modifications alter the efficiency and fidelity of translation (,,,,) and turnover of transcripts in the actively translating mRNA pool (,,).
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References

    1. DAVIS FF, ALLEN FW. Ribonucleic acids from yeast which contain a fifth nucleotide. J. Biol. Chem. 1957;227:907–15. - PubMed
    1. Machnicka MA, et al. MODOMICS: a database of RNA modification pathways–2013 update. Nucleic Acids Res. 2013;41:D262–7. - PMC - PubMed
    1. Perry RP, Kelley DE. Existence of methylated messenger RNA in mouse L cells. Cell. 1974;1:37–42.
    1. Desrosiers R, Friderici K, Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc. Natl. Acad. Sci. U. S. A. 1974;71:3971–5. - PMC - PubMed
    1. Dominissini D, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012;485:201–6. - PubMed

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