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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.
Pubmed ID: 30449621 RIS Download
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View all literature mentionsSoftware Python package for identifying transcript factor binding sites. Used to evaluate significance of enriched ChIP regions. Improves spatial resolution of binding sites through combining information of both sequencing tag position and orientation. Can be used for ChIP-Seq data alone, or with control sample with increase of specificity.
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View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
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View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsUltrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.
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View all literature mentionsThis monoclonal targets bromodeoxyuridine
View all literature mentionsThis polyclonal targets NAT10
View all literature mentionsThis polyclonal targets EEF1A1
View all literature mentionsThis monoclonal targets Histone H3
View all literature mentionsThis monoclonal targets Acetyl-α-Tubulin (Lys40)
View all literature mentionsThis monoclonal targets alpha-Tubulin
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis polyclonal targets eIF2 alpha
View all literature mentionsThis unknown targets NAT10
View all literature mentionsThis monoclonal targets GAPDH (6C5)
View all literature mentionsThis polyclonal targets HNRNPD
View all literature mentionsThis monoclonal targets hnRNP L antibody [4D11]
View all literature mentionsThis isotype control targets not applicable
View all literature mentionsThis isotype control targets not applicable
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets A synthetic phospho-peptide corresponding to residues surrounding Ser51 of human EIF2S1.
View all literature mentionsThis monoclonal secondary targets IgG
View all literature mentionsThis polyclonal targets FUS
View all literature mentionsThis monoclonal targets RpII215
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis polyclonal targets Histone H3 (acetyl K9 + K14 + K18 + K23 + K27) antibody - ChIP Grade
View all literature mentionsThis polyclonal targets Donkey anti-Rabbit IgG H&L (DyLight® 488) secondary antibody
View all literature mentionsThis monoclonal targets hnRNP A2B1
View all literature mentionsThis monoclonal targets Human p53 (acetyl K120)
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