Maternal N-acetyltransferase 10 (NAT10) orchestrates oocyte meiotic cell-cycle progression and maturation in mice

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 during oocyte development remain largely unclear. Here we characterized the function of N-acetyltransferase 10 (Nat10), which was previously recognized as a “writer” for N4-acetylcytidine (ac4C) deposited on RNA molecules. We generated two germline-specific Nat10 knockout mouse models in the embryonic gonad and in postnatal growing oocytes, and another two tamoxifen-inducible Nat10 deletion models. We provided genetic evidence showing that Nat10 is essential for oocyte meiotic prophase I progression, oocyte growth and maturation in mice. Intriguingly, we discovered that Nat10 is required for sculpting the maternal transcriptome through timely degradation of polyA tail mRNAs during the Maternal-to-Zygotic transition (MZT). Importantly, we developed a novel method that outperformed the conventional methods for examining the polyA tail length (PAT), termed Hairpin Adaptor-polyA tail length (HA-PAT), in terms of the cost, sensitivity and efficiency. In summary, these findings altogether provide solid genetic evidence that unveils the indispensable role of maternal Nat10 in oocyte development, and lay a solid foundation for future mechanistic studies of varied domains of NAT10.