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RNA Cytidine Acetyltransferase NAT10 Maintains T Cell Pathogenicity in Inflammatory Bowel Disease

ABSTRACT: RNA Cytidine Acetyltransferase NAT10 Maintains T Cell Pathogenicity in Inflammatory Bowel Disease

PROVIDER: PRJNA1200084 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31767653.fastq.gz	Fastqsanger.gz
	SRR31767653_1.fastq.gz	Fastqsanger.gz
	SRR31767653_2.fastq.gz	Fastqsanger.gz
	SRR31767654.fastq.gz	Fastqsanger.gz
	SRR31767654_1.fastq.gz	Fastqsanger.gz

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Project description: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. 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 a novel mRNA modification that is catalyzed by the acetyltransferase NAT10. Transcriptome-wide mapping of ac4C revealed discretely acetylated regions that were distributed across target mRNAs with the majority of peaks occurring within coding regions. Depletion of ac4C through NAT10 ablation revealed a relationship to gene expression wherein loss of ac4C was globally associated with transcript downregulation. The presence of ac4C within coding sequences was associated with elevated ribosome density and enhanced translation, as assessed in vivo and in vitro. In addition to expanding the repertoire of mRNA modifications to include an acetylated residue, these findings highlight a role for ac4C in the control of mRNA metabolism at the level of translation.

Dataset Information

RNA Cytidine Acetyltransferase NAT10 Maintains T Cell Pathogenicity in Inflammatory Bowel Disease

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