The RNA ac4C Writer NAT10-dependent Post-transcriptional Regulations are Prerequisites for Zygotic Splicing Activation in Mouse

N4-acetylcytidine (ac4C) is a conserved post-transcriptional RNA modification catalyzed by the only known “writer”, N-acetyltransferase 10 (NAT10), but its landscape and function in early embryos remain further exploration owing to limited materials.

In this study, we characterized the ac4C modification reprogramming dynamics throughout preimplantation embryogenesis and identified that Nat10 ablation from primary follicle oocytes leads to female infertility with embryonic arrest at the 2-cell transition. Notably, we found that the maternal protein NAT10 was essential for ac4C deposition on ZGA transcripts and maternal mRNAs, and the loss of Nat10 could also lead to abnormal accumulation of maternal transcripts and major ZGA inactivation.