@article{8e12d426d14d48c5aae1d0175079418d,
title = "Acetylation of Cytidine in mRNA Promotes Translation Efficiency",
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.",
keywords = "N4-acetylcytidine, NAT10, epitranscriptome, mRNA stability, mRNA translation",
author = "Daniel Arango and David Sturgill and Najwa Alhusaini and Dillman, {Allissa A.} and Sweet, {Thomas J.} and Gavin Hanson and Masaki Hosogane and Sinclair, {Wilson R.} and Nanan, {Kyster K.} and Mandler, {Mariana D.} and Fox, {Stephen D.} and Zengeya, {Thomas T.} and Thorkell Andresson and Meier, {Jordan L.} and Jeffery Coller and Shalini Oberdoerffer",
note = "Funding Information: We thank the members of the Center for Cancer Research Sequencing Facility at the National Cancer Institute (Frederick, MD) for providing Illumina sequencing services. We thank Dr. Lin Qishan from the Mass Spectrometry Center at the RNA Institute SUNY-Albany (Albany, NY) for providing LC-MS/MS services. This study utilized the Biowulf Linux cluster at the NIH, Bethesda, MD (https://hpc.nih.gov). This work is supported by the Intramural Research Program of the National Institutes of Health (NIH), NCI, Center for Cancer Research. Support for J.C. was provided by the NIH (GM118018, GM125086). Funding Information: We thank the members of the Center for Cancer Research Sequencing Facility at the National Cancer Institute (Frederick, MD) for providing Illumina sequencing services. We thank Dr. Lin Qishan from the Mass Spectrometry Center at the RNA Institute SUNY-Albany (Albany, NY) for providing LC-MS/MS services. This study utilized the Biowulf Linux cluster at the NIH, Bethesda, MD ( https://hpc.nih.gov ). This work is supported by the Intramural Research Program of the National Institutes of Health (NIH) , NCI , Center for Cancer Research . Support for J.C. was provided by the NIH ( GM118018 , GM125086 ). Publisher Copyright: {\textcopyright} 2018",
year = "2018",
month = dec,
day = "13",
doi = "10.1016/j.cell.2018.10.030",
language = "English (US)",
volume = "175",
pages = "1872--1886.e24",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",
}