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NAT10-mediated N4-acetylcytidine mRNA Modification Regulates Self-Renewal in Human Embryonic Stem Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226752 | GEO | 2023/08/25

REPOSITORIES: GEO

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NAT10-mediated N4 acetylcytidine(ac4C) mRNA Modification Regulates Self-Renewal in Human Embryonic Stem Cells

Project description:NAT10-mediated N4 acetylcytidine(ac4C) mRNA Modification Regulates Self-Renewal in Human Embryonic Stem Cells

| PRJNA809481 | ENA

Function and Mechanism of NAT10-mediated N4-acetylcytidine modification in osteosarcoma [mRNA-seq]

Project description:Despite the advance in diagnosis and treatment, the prognosis of osteosarcoma patients remains unsatisfied. Therefore, it is imperative to identify novel therapeutic targets for osteosarcoma. Through RNA sequencing (RNA-seq) combined with functional screening, N4-acetylcytidine (ac4C) acetyltransferase 10 (NAT10) was identified as a candidate therapeutic target in osteosarcoma. Upregulated NAT10 correlated with poor prognosis in osteosarcoma patients and NAT10 knockout drastically inhibited cell proliferation and metastasis in vitro and in vivo. NAT10 enhanced mRNA stability and translation efficiency of activating transcription factor 4 (ATF4) through ac4C modification. ATF4 induced transcription of asparagine synthetase (ASNS), which catalyzes asparagine (Asn) biosynthesis. Asn promote protein and nucleotide synthesis, facilitating osteosarcoma progression. Overexpression of ATF4, ASNS or supplementation of asparagine rescue the tumor inhibitory effect of NAT10 knockout.

2024-08-09 | GSE237541 | GEO

PACES: prediction of N4-acetylcytidine (ac4C) modification sites in mRNA.

Project description: Not available

| S-EPMC6668381 | biostudies-literature

NAT10 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Mediating N4-Acetylcytidine Modification of Gremlin 1.

Project description: Not available

| S-EPMC8057913 | biostudies-literature

Function and Mechanism of NAT10-mediated N4-acetylcytidine modification in osteosarcoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-08-09 | GSE237543 | GEO

Function and Mechanism of NAT10-mediated N4-acetylcytidine modification in osteosarcoma [RIP-seq]

2024-08-09 | GSE237840 | GEO

NAT10-Mediated N4-Acetylcytidine of RNA Contributes to Post-transcriptional Regulation of Mouse Oocyte Maturation <i>in vitro</i>.

Project description: Not available

| S-EPMC8363255 | biostudies-literature

NAT10-mediated N4-Acetylcytidine is Required for Spermatogenesis and Male Fertility

Project description:RNA modifications are rapidly emerging as critical post-transcriptional regulators which play a key role in various biological processes. N4-acetylcysteine (ac4C) is one of the “epi-transcriptome” that is present on tRNA, rRNA, mRNA and is also highly conserved in all species. However, cytidine acetylation's in vivo physiological functions remain poorly understood particularly in mammals. Here we demonstrate only known ac4C “writer”—N-acetyltransferase 10 (NAT10) plays essential roles in male reproduction. NAT10 protein and the ac4C modification have different patterns in different organs and there are dynamic changes during spermatogenesis. Germ cell-specific ablation of NAT10 severely inhibited meiotic entry and defects in synapse the homologous chromosomes, repair of DNA double-strand breaks (DSBs) during prophase of the first meiotic division. ac4C RIP-qPCR reveals genes functioning in meiotic prophase I show a decrease in Nat10fl/-; Stra8 GFP-Cre mouse testes. These findings highlight the crucial physiological functions of mRNA ac4C modification in male spermatogenesis and expand our understanding of mRNA ac4C modification in the regulation of specific physiological processes in vivo.

2022-11-16 | GSE191105 | GEO

N4-acetylcytidine (ac4C) promotes mRNA localization to stress granules

Project description: Not available

| S-SCDT-10_1038-S44319-024-00098-6 | biostudies-other

NAT10-mediated mRNA N4-acetylcytidine is Essential for the Translational Regulation of Oocyte Meiotic Maturation in Mice

Project description:Mammalian oocyte maturation is driven by strictly translational regulation of maternal mRNAs stored in the cytoplasm. However, the function and mechanism of post-transcriptional chemical modifications especially the newly identified N4-acetylcytidine (ac4C) catalyzed by N-acetyltransferase 10 (NAT10) in this process are previously unknown. In this study, we developed a low-input ac4C sequencing technology - ac4C LACE-seq and mapped 8241 ac4C peaks at the whole transcriptome level using 50 mouse oocytes at the germinal vesicle (GV) stage. We profiled the mRNA landscapes of NAT10-interactions and ac4C modifications. The NAT10-interacted and ac4C modified transcripts displayed association with high translation efficiency in oocytes. Oocyte-specific Nat10 knockout wiped out ac4C signals in oocytes and caused severe defects in meiotic maturation and female infertility. ac4C LACE-seq results indicated that Nat10 deletion led to a failure of ac4C deposition on mRNAs encoding key maternal factors such as MAY2, ZAR1, BTG4 and cyclin B1 that regulate transcriptome stability and maternal-to-zygotic transition. Nat10-deleted oocytes had decreased mRNA translation efficiencies during meiotic maturation, partially due to the direct inhibition ac4C sites on specific transcripts. In sum, we developed low-input, high-sensitivity mRNA ac4C profiling approach and highlighted the important physiological function of ac4C in precise regulation of the oocyte meiotic maturation by enhancing translation efficiency.

2024-08-26 | GSE253976 | GEO

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