N-6-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.

Automated summary

The study reveals the unique enrichment and dynamics of m(6)A RNA modifications in mouse oocytes and early embryos, impacting the stability and decay of transcripts. METTL3, an m(6)A methyltransferase, plays a crucial role in depositing m(6)A on two-cell-specific transcripts Zscan4 and MERVL.