NAT10-mediated mRNA N 4 -acetylation is essential for the translational regulation during oocyte meiotic maturation in mice

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-02-21 DOI:10.1126/sciadv.adp5163

Lu Chen, Wen-Jing Wang, Shao-Yuan Liu, Rui-Bao Su, Yu-Ke Wu, Xuan Wu, Song-Ying Zhang, Jie Qiao, Qian-Qian Sha, Heng-Yu Fan

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Abstract

The precise translational regulation of maternal messenger RNAs (mRNAs) drives mammalian oocyte maturation. However, the function and mechanism of posttranscriptional chemical modifications, especially the newly identified N 4 -acetylcytidine (ac 4 C) modification catalyzed by N -acetyltransferase 10 (NAT10), are unknown. In this study, we developed a low-input ac 4 C sequencing technology, ac 4 C LACE-seq, and mapped 8241 ac 4 C peaks at the whole-transcriptome level using 50 mouse oocytes at the germinal vesicle stage. Oocyte-specific Nat10 knockout wiped out ac 4 C signals in oocytes and caused severe defects in meiotic maturation and female infertility. Mechanically, Nat10 deletion led to a failure of ac 4 C deposition on mRNAs encoding key maternal factors, which regulate transcriptome stability and maternal-to-zygotic transition. Nat10 -deleted oocytes showed decreased mRNA translation efficiency due to the direct inhibition of ac 4 C sites on specific transcripts during meiotic maturation. In summary, we developed a low-input, high-sensitivity mRNA ac 4 C profiling approach and highlighted the important physiological function of ac 4 C in the precise regulation of oocyte meiotic maturation by enhancing translation efficiency.

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nat10介导的mRNA N 4乙酰化对小鼠卵母细胞减数分裂成熟过程中的翻译调控至关重要

母体信使rna （mrna）的精确翻译调控驱动哺乳动物卵母细胞成熟。然而，转录后化学修饰的功能和机制，特别是新发现的由N -乙酰基转移酶10 （NAT10）催化的4 -乙酰胞苷（ac4c）修饰尚不清楚。在这项研究中，我们开发了一种低输入ac 4c测序技术，ac 4c LACE-seq，并在全转录组水平上绘制了50个小鼠卵母细胞在生发囊泡期的8241个ac 4c峰。卵母细胞特异性的Nat10敲除消除了卵母细胞中的ac4c信号，导致减数分裂成熟和女性不育的严重缺陷。从机械上讲，Nat10缺失导致编码关键母体因子的mrna上的ac 4c沉积失败，这些因子调节转录组稳定性和母体到合子的转变。由于在减数分裂成熟过程中特定转录本上的ac4c位点受到直接抑制，Nat10缺失的卵母细胞mRNA翻译效率下降。总之，我们开发了一种低输入、高灵敏度的mRNA ac 4c分析方法，并强调了ac 4c通过提高翻译效率在精确调节卵母细胞减数分裂成熟中的重要生理功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.