Maternal N-acetyltransferase 10 (NAT10) orchestrates oocyte meiotic cell-cycle progression and maturation in mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE228721 | GEO | 2023/04/04
REPOSITORIES: GEO
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Project description: Not available
| S-EPMC10287700 | biostudies-literature
Project description:Maternal N-acetyltransferase 10 (NAT10) orchestrates oocyte meiotic cell-cycle progression and maturation in mice
| PRJNA951361 | ENA
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
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.
2024-02-18 | GSE254288 | GEO
Project description:Here, we show that NAT10 is an essential regulator of cellular plasticity, and its catalyzed mRNA cytidine acetylation represents a new layer of epitranscriptomic modulation.
2023-11-14 | PXD036888 | Pride
Project description:The enzyme N-acetyltransferase 10 (NAT10), known as the exclusive catalyst for N4-acetylcytidine (ac4C) modification, has been associated with various cellular processes, including tRNA acetylation, 18S rRNA biogenesis, mRNA stability, and translational efficiency. Despite extensive investigation into its molecular mechanisms in vitro, the physiological function of NAT10 under normal conditions has remained largely undefined. In this study, we found that the deficiency of NAT10 led to a disruption of T cell development at steady state, and identified a pivotal role for NAT10 in preserving the pathogenicity of naïve CD4+ T cells to induce adoptive transfer colitis. Mechanistically, the lack of NAT10 triggers the diminished stability of the anti-apoptotic gene Bag3, initiating a cascade of events that includes the upregulation of apoptosis-related genes and an accelerated rate of apoptosis in T cells. Our findings reveal a previously unrecognized role of the NAT10-ac4C-Bag3 axis in maintaining T cell homeostasis in vivo.
2025-03-12 | GSE284711 | GEO
Project description:We show that NAT10-ac4C axis significantly regulates cell fates. To identify the molecular mechanisms of NAT10-ac4C-ANP32B axis in cell-fate transitions, we construct shNAT10 and shANP32B hESCs. acRIP-seq of shCTR and shNAT10 hESCs. We profiled ATAC-seq in shCTR, shNAT10, and shANP32B hESCs. We profiled H3K4me3 and H3K27me3 modifications and the binding of ANP32B by CUT&Tag in shCTR and shNAT10 hESCs.
2023-11-11 | GSE210504 | GEO
Project description:Zar1 was the first mammalian maternal-effect gene to be identified. Embryos derived from Zar1-null female mice are blocked before zygotic genome activation; however, the underlying mechanism remains unclear. By knocking out Zar1 and its homolog Zar2 in mice, we revealed a novel function of these genes in oocyte meiotic maturation. Zar1/2-deleted oocytes displayed delayed meiotic resumption and polar body-1 emission and a higher incidence of abnormal meiotic spindle formation and chromosome aneuploidy. The grown oocytes of Zar1/2-null mice contained fewer total mRNAs and displayed a reduced level of protein synthesis. Key maturation-associated changes failed to occur in the Zar1/2-null oocytes, including the translational activation of maternal mRNAs encoding the cell cycle proteins cyclin B1 and WEE2, as well as maternal-to-zygotic transition (MZT) licensing factor BTG4. Consequently, maternal mRNA decay was impaired and MZT was abolished. ZAR1/2 bound mRNAs to regulate the translational activity of their 3ʹ-UTRs and interacted with other oocyte proteins, including mRNA-stabilizing protein MSY2 and cytoplasmic lattice components. These results countered the traditional view that ZAR1 only functions after fertilization and highlight a previously unrecognized role of ZAR1/2 in regulating the maternal transcriptome and translational activation in maturing oocytes.
2019-09-25 | GSE135787 | GEO
Project description:The enzyme N-acetyltransferase 10 (NAT10), known as the exclusive catalyst for N4-acetylcytidine (ac4C) modification, has been associated with various cellular processes, including tRNA acetylation, 18S rRNA biogenesis, mRNA stability, and translational efficiency. Despite extensive investigation into its molecular mechanisms in vitro, the physiological function of NAT10 under normal conditions has remained largely undefined. In this study, we found that the deficiency of NAT10 led to a disruption of T cell development at steady state, and identified a pivotal role for NAT10 in preserving the pathogenicity of naïve CD4+ T cells to induce adoptive transfer colitis. Mechanistically, the lack of NAT10 triggers the diminished stability of the anti-apoptotic gene Bag3, initiating a cascade of events that includes the upregulation of apoptosis-related genes and an accelerated rate of apoptosis in T cells. Our findings reveal a previously unrecognized role of the NAT10-ac4C-Bag3 axis in maintaining T cell homeostasis in vivo.
2025-03-12 | GSE285309 | GEO
Project description:The control of gene expression program is believed to underlie hematopoietic stem cell (HSC) homeostasis. However, a comprehensive molecular understanding of the RNA level regulation is currently lacking. Here we provide evidence that the HSC-associated transcripts have longer 3’UTRs and more enriched AU-rich elements (AREs), which were recognized by Nat10. Nat10 is highly expressed in HSC and its deficiency disrupts HSC self-renewal and long-term maintenance. In contrast to current model that invoke ac4C modification to mediate downstream effects, we find Nat10 recruits ribosomes to mRNA 3’UTRs and protects them from degradation by ZFP36-CNOT RNA decay complex. Nat10 depletion leads to reduction of mRNA hail-life, and both wild-type and catalytically inactive Nat10 promote the stability of mRNA with AREs. We present a model that Nat10 regulates mRNA stability as an ARE-binding protein rather than ac4C writer in HSC, a mechanism is required for hematopoietic homeostasis, highlighting the importance of transcript-specific characteristics determining the contribution of Nat10 in HSC fate.
2026-03-21 | GSE276136 | GEO