The RNA m6A landscape during human oocyte-to-embryo transition

RNA N(6)-methyladenosine (m(6)A, m6A) modification is a critical regulator for a range of physiological processes. However, the dynamic m(6)A profiles within human preimplantation embryos remain uncharacterized. Here, we present the first RNA m(6)A landscape of single human oocytes and early embryos. Comparative analyses with mouse data reveal an intriguing divergence during the window of zygotic genome activation. m(6)A-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 m(6)A modifications, and these genes are targeted by miRNAs. m(6)A modified genes that are constantly expressed across all stages demonstrate higher translation efficiency. Moreover, we observe frequent m(6)A enrichment on stage-specifically expressed retrotransposons, particularly within young subfamilies. m(6)A inhibitor leads to m(6)A erasure on massive retrotransposons. In summary, this study provides a resource to broaden our understanding about the regulatory roles of m(6)A during early human embryo development.