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Acetylation of Cytidine in mRNA Promotes Translation Efficiency
Ist Teil von
Cell, 2018-12, Vol.175 (7), p.1872-1886.e24
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2018
Quelle
Elsevier ScienceDirect Journals
Beschreibungen/Notizen
Generation of the “epitranscriptome” through post-transcriptional ribonucleoside modification embeds a layer of regulatory complexity into RNA structure and function. Here, we describe N4-acetylcytidine (ac4C) as an mRNA modification that is catalyzed by the acetyltransferase NAT10. Transcriptome-wide mapping of ac4C revealed discretely acetylated regions that were enriched within coding sequences. Ablation of NAT10 reduced ac4C detection at the mapped mRNA sites and was globally associated with target mRNA downregulation. Analysis of mRNA half-lives revealed a NAT10-dependent increase in stability in the cohort of acetylated mRNAs. mRNA acetylation was further demonstrated to enhance substrate translation in vitro and in vivo. Codon content analysis within ac4C peaks uncovered a biased representation of cytidine within wobble sites that was empirically determined to influence mRNA decoding efficiency. These findings expand the repertoire of mRNA modifications to include an acetylated residue and establish a role for ac4C in the regulation of mRNA translation.
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•NAT10 catalyzes N4-acetylcytidine (ac4C) modification of a broad range of mRNAs•mRNA acetylation within coding sequences promotes translation and mRNA stability•ac4C in wobble sites stimulates translation efficiency
Post-transcriptional acetylation of cytidines in mammalian mRNAs enhances RNA stability and translation.