Acetylation of Cytidine in mRNA Promotes Translation Efficiency

Daniel Arango, David Sturgill, Najwa Alhusaini, Allissa A. Dillman, Thomas J. Sweet, Gavin Hanson, Masaki Hosogane, Wilson R. Sinclair, Kyster K. Nanan, Mariana D. Mandler, Stephen D. Fox, Thomas T. Zengeya, Thorkell Andresson, Jordan L. Meier, Jeffery Coller, Shalini Oberdoerffer

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1872-1886.e24
JournalCell
Volume175
Issue number7
DOIs
StatePublished - Dec 13 2018
Externally publishedYes

Keywords

  • N4-acetylcytidine
  • NAT10
  • epitranscriptome
  • mRNA stability
  • mRNA translation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'Acetylation of Cytidine in mRNA Promotes Translation Efficiency'. Together they form a unique fingerprint.

Cite this