Abstract
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 N4-acetylcytidine (ac4C) modification catalyzed by N-acetyltransferase 10 (NAT10), are unknown. In this study, we developed a low-input ac4C sequencing technology, ac4C LACE-seq, and mapped 8241 ac4C peaks at the whole-transcriptome level using 50 mouse oocytes at the germinal vesicle stage. Oocyte-specific Nat10 knockout wiped out ac4C signals in oocytes and caused severe defects in meiotic maturation and female infertility. Mechanically, Nat10 deletion led to a failure of ac4C 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 ac4C sites on specific transcripts during meiotic maturation. In summary, we developed a low-input, high-sensitivity mRNA ac4C profiling approach and highlighted the important physiological function of ac4C in the precise regulation of oocyte meiotic maturation by enhancing translation efficiency.