卵母细胞
乙酰化
减数分裂
信使核糖核酸
细胞生物学
生物
翻译(生物学)
化学
遗传学
基因
胚胎
作者
Lu Chen,Wen-Jing Wang,Shao-Yuan Liu,Ruibao Su,Yu-Ke Wu,Xuan Wu,Songying Zhang,Jie Qiao,Qian‐Qian Sha,Heng‐Yu Fan
出处
期刊:Science Advances
[American Association for the Advancement of Science]
日期:2025-02-21
卷期号:11 (8)
标识
DOI:10.1126/sciadv.adp5163
摘要
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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