Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice
Xue Jiang, Yu Cheng, Yu Zhu, Caoling Xu, Qiaodan Li, Xuemei Xing, Wenqing Li, Jiaqi Zou, Meng Lan, Muhammad Azhar, Yuzhu Cao, Xianhong Tong, Weibing Qin, Xiaoli Zhu, Jianqiang Bao
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.