Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice.
Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice.
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DOI：
10.1038/s41467-023-39256-0
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发表时间：
2023-06-22
影响因子：
16.6
通讯作者：
Bao, Jianqiang
中科院分区：
文献类型：
--
作者：
Jiang, Xue;Cheng, Yu;Zhu, Yuzhang;Xu, Caoling;Li, Qiaodan;Xing, Xuemei;Li, Wenqing;Zou, Jiaqi;Meng, Lan;Azhar, Muhammad;Cao, Yuzhu;Tong, Xianhong;Qin, Weibing;Zhu, Xiaoli;Bao, Jianqiang
在哺乳动物中，成熟卵母细胞的产生需要在转录和转录后水平上严格调控不连续的减数分裂细胞周期进程。然而，这一复杂而明确的过程背后的因素在很大程度上仍不清楚。在这里，我们的特点N-乙酰转移酶10（Nat 10），作家N4-乙酰胞苷（ac 4C）的RNA分子，在小鼠卵母细胞发育的功能。我们提供了遗传学证据，证明Nat 10是卵母细胞减数分裂前期I进程，卵母细胞生长和成熟所必需，通过及时降解poly（A）尾mRNA来雕刻母体转录组。这是通过ac 4C沉积在关键的CCR 4-NOT复合物转录本上实现的。重要的是，我们设计了一种用于检查poly（A）尾长（PAT）的方法，称为发夹衔接子-poly（A）尾长（HA-PAT），其在成本、灵敏度和效率方面优于常规方法。总之，这些发现提供了遗传学证据，揭示了母体Nat 10在卵母细胞发育中不可或缺的作用。成熟卵母细胞的产生需要严格调控不连续的减数分裂细胞周期。在这里，他们表明乙酰转移酶Nat 10介导了针对降解的RNA的修饰，并发现这一过程对雌性卵母细胞减数分裂和成熟至关重要。
In mammals, the production of mature oocytes necessitates rigorous regulation of the discontinuous meiotic cell-cycle progression at both the transcriptional and post-transcriptional levels. However, the factors underlying this sophisticated but explicit process remain largely unclear. Here we characterize the function of N-acetyltransferase 10 (Nat10), a writer for N4-acetylcytidine (ac4C) on RNA molecules, in mouse oocyte development. We provide genetic evidence that Nat10 is essential for oocyte meiotic prophase I progression, oocyte growth and maturation by sculpting the maternal transcriptome through timely degradation of poly(A) tail mRNAs. This is achieved through the ac4C deposition on the key CCR4-NOT complex transcripts. Importantly, we devise a method for examining the poly(A) tail length (PAT), termed Hairpin Adaptor-poly(A) tail length (HA-PAT), which outperforms conventional methods in terms of cost, sensitivity, and efficiency. In summary, these findings provide genetic evidence that unveils the indispensable role of maternal Nat10 in oocyte development. Generation of mature oocytes requires tight regulation of a discontinuous meiotic cell cycle. Here they show that the acetyltransferase Nat10 mediates modification of RNAs targeted for degradation and find that this process is essential for female oocyte meiosis and maturation.
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