| First Author | Chen L | Year | 2025 |
| Journal | Sci Adv | Volume | 11 |
| Issue | 8 | Pages | eadp5163 |
| PubMed ID | 39982985 | Mgi Jnum | J:361945 |
| Mgi Id | MGI:7867307 | Doi | 10.1126/sciadv.adp5163 |
| Citation | Chen L, et al. (2025) NAT10-mediated mRNA N(4)-acetylation is essential for the translational regulation during oocyte meiotic maturation in mice. Sci Adv 11(8):eadp5163 |
| abstractText | 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 N(4)-acetylcytidine (ac(4)C) modification catalyzed by N-acetyltransferase 10 (NAT10), are unknown. In this study, we developed a low-input ac(4)C sequencing technology, ac(4)C LACE-seq, and mapped 8241 ac(4)C peaks at the whole-transcriptome level using 50 mouse oocytes at the germinal vesicle stage. Oocyte-specific Nat10 knockout wiped out ac(4)C signals in oocytes and caused severe defects in meiotic maturation and female infertility. Mechanically, Nat10 deletion led to a failure of ac(4)C 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 ac(4)C sites on specific transcripts during meiotic maturation. In summary, we developed a low-input, high-sensitivity mRNA ac(4)C profiling approach and highlighted the important physiological function of ac(4)C in the precise regulation of oocyte meiotic maturation by enhancing translation efficiency. |
