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

RNA N⁶-methyladenosine (m⁶A, m6A) modification is a critical regulator for a range of physiological processes. However, the dynamic m⁶A profiles within human preimplantation embryos remain uncharacterized. Here, we present the first RNA m⁶A landscape of single human oocytes and early embryos. Comparative analyses with mouse data reveal an intriguing divergence during the window of zygotic genome activation. m⁶A-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 m⁶A modifications, and these genes are targeted by miRNAs. m⁶A modified genes that are constantly expressed across all stages demonstrate higher translation efficiency. Moreover, we observe frequent m⁶A enrichment on stage-specifically expressed retrotransposons, particularly within young subfamilies. m⁶A inhibitor leads to m⁶A erasure on massive retrotransposons. In summary, this study provides a resource to broaden our understanding about the regulatory roles of m⁶A during early human embryo development.