Reading and writing of mRNA m6A modification orchestrate maternal-to-zygotic transition in mice

N 6 -methyladenosine (m 6 A) modification has been shown to regulate RNA metabolism. Here, we investigate m 6 A dynamics during maternal-to-zygotic transition (MZT) in mice through multi-omic analysis. Our results show that m 6 A can be maternally inherited or de novo gained after fertilization. Interestingly, m 6 A modification on maternal mRNAs not only correlates with mRNA degradation, but also maintains the stability of a small group of mRNAs thereby promoting their translation after fertilization. We identify Ythdc1 and Ythdf2 as key m 6 A readers for mouse preimplantation development. Our study reveals a key role of m 6 A mediated RNA metabolism during MZT in mammals.