Li Yanjiao, Wang Yunhao, Cengiz Aylin, Jin Kang-Xuan, Castroviejo Blanca Corral, Lin Xiaolin, Indahl Marie, Zuo Rujuan, Skuland Trine, Fosslie Madeleine, Biba Maria, Wu Xuechen, Fedorcsak Peter, Bjørås Magnar, Filipczyk Adam, Dahl John Arne, Greggains Gareth D, Au Kin Fai, Klungland Arne
Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway.
EMBO J. 2025 Jun 4. doi: 10.1038/s44318-025-00474-5.
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.
RNA N-甲基腺苷（mA，m6A）修饰是一系列生理过程的关键调节因子。然而，人类植入前胚胎内的动态mA图谱仍未得到表征。在此，我们展示了首个单个人类卵母细胞和早期胚胎的RNA mA图谱。与小鼠数据的比较分析揭示了合子基因组激活窗口期间的一个有趣差异。mA修饰的基因参与基因转录调控，而未修饰的基因主要与基本代谢过程相关。母体降解mRNA表现出mA修饰的倾向，并且这些基因是miRNA的靶标。在所有阶段持续表达的mA修饰基因表现出更高的翻译效率。此外，我们观察到阶段特异性表达的逆转座子上频繁出现mA富集，特别是在年轻亚科内。mA抑制剂导致大量逆转座子上的mA消除。总之，本研究提供了一种资源，以拓宽我们对mA在人类早期胚胎发育过程中调节作用的理解。
