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

N6-methyladenosine (m6A) and its regulatory components play critical roles in various developmental processes in mammals. However, the landscape and function of m6A in early embryos remain unclear owing to limited materials. Here we developed a method of ultralow-input m6A RNA immunoprecipitation followed by sequencing to reveal the transcriptome-wide m6A landscape in mouse oocytes and early embryos and found unique enrichment and dynamics of m6A 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 m6A methyltransferase complex, was essential for m6A deposition on maternal mRNAs that undergo decay after zygotic genome activation and MTA transcripts to maintain their stability in oocytes. Interestingly, m6A methyltransferases, especially METTL3, deposited m6A 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 m6A 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 m6A mapping method for ultralow-input materials and characterized the transcriptome-wide landscape of m6A methylation in mouse oocytes and early embryos.