Acetylation of cytidine in messenger RNA promotes translation efficiency

By Daniel Arango, David Sturgill, Najwa Alhusaini, Allissa Dillman, Thomas J. Sweet, Gavin Hanson, Masaki Hosogane, Wilson R. Sinclair, K. Nanan, Mariana D. Mandler and 6 more. Cell, 2018

690 citations recorded by the source corpus.

Summary 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 down-regulation. 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/574f0c32337a89d2438d1eb898235f45e020f0ca