N6-methyladenosine regulates maternal RNA maintenance in oocytes and timely RNA decay during mouse maternal-to-zygotic transition

N 6 -methyladenosine (m 6 A) and its regulatory components play critical roles in various developmental processes in mammals. However, the landscape and function of m 6 A in early embryos remain unclear owing to limited materials. Here we developed a method of ultralow-input m 6 A RNA immunoprecipitation followed by sequencing to reveal the transcriptome-wide m 6 A landscape in mouse oocytes and early embryos and found unique enrichment and dynamics of m 6 A RNA modifications on maternal and zygotic RNAs, including the transcripts of transposable elements MTA and MERVL. Notably, we found that the maternal protein KIAA1429, a component of the m 6 A methyltransferase complex, was essential for m 6 A deposition on maternal mRNAs that undergo decay after zygotic genome activation and MTA transcripts to maintain their stability in oocytes. Interestingly, m 6 A methyltransferases, especially METTL3, deposited m 6 A on mRNAs transcribed during zygotic genome activation and ensured their decay after the two-cell stage, including Zscan4 and MERVL. Together, our findings uncover the essential functions of m 6 A in specific contexts during the maternal-to-zygotic transition, namely ensuring the stability of mRNAs in oocytes and the decay of two-cell-specific transcripts after fertilization. Wu et al. optimized the m 6 A mapping method for ultralow-input materials and characterized the transcriptome-wide landscape of m 6 A methylation in mouse oocytes and early embryos.