The RNA mA landscape during human oocyte-to-embryo transition.

RNA N-methyladenosine (mA, m6A) modification is a critical regulator for a range of physiological processes. However, the dynamic mA profiles within human preimplantation embryos remain uncharacterized. Here, we present the first RNA mA landscape of single human oocytes and early embryos. Comparative analyses with mouse data reveal an intriguing divergence during the window of zygotic genome activation. mA-modified genes are involved in regulation of gene transcription, while unmodified genes are mainly associated with basic metabolic processes. Maternal decay mRNAs exhibit a propensity for mA modifications, and these genes are targeted by miRNAs. mA modified genes that are constantly expressed across all stages demonstrate higher translation efficiency. Moreover, we observe frequent mA enrichment on stage-specifically expressed retrotransposons, particularly within young subfamilies. mA inhibitor leads to mA erasure on massive retrotransposons. In summary, this study provides a resource to broaden our understanding about the regulatory roles of mA during early human embryo development.