Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice

  • Nat Commun. 2023 Jun 22;14(1):3729. doi: 10.1038/s41467-023-39256-0.
Xue Jiang  #  1 ,  Yu Cheng  #  2 ,  Yuzhang Zhu  #  3 ,  Caoling Xu  #  1 ,  Qiaodan Li  4 ,  Xuemei Xing  5 ,  Wenqing Li  1 ,  Jiaqi Zou  1 ,  Lan Meng  1 ,  Muhammad Azhar  1 ,  Yuzhu Cao  5 ,  Xianhong Tong  5 ,  Weibing Qin  6 ,  Xiaoli Zhu  7 ,  Jianqiang Bao  8  9
Affiliations
  • 1. Reproductive and Genetic Hospital, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), 230001, Hefei, Anhui, China.
  • 2. School of Information Science and Technology, University of Science and Technology of China (USTC), 230001, Hefei, Anhui, China.
  • 3. Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), 230001, Hefei, Anhui, China.
  • 4. Laboratory animal center, University of Science and Technology of China (USTC), 230001, Hefei, Anhui, China.
  • 5. Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), 230001, Hefei, Anhui, China.
  • 6. NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), 510600, Guangzhou, China. [email protected].
  • 7. Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), 230001, Hefei, Anhui, China. [email protected].
  • 8. Reproductive and Genetic Hospital, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), 230001, Hefei, Anhui, China. [email protected].
  • 9. Hefei National Research Center for Physical Sciences at the Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China (USTC), 230001, Hefei, Anhui, China. [email protected].
  • # Contributed equally.
PMID: 37349316 DOI: 10.1038/s41467-023-39256-0
Abstract

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.

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