Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Nat Struct Mol Biol. 2023 May;30(5):703-709. doi: 10.1038/s41594-023-00969-x. Epub 2023 Apr 20.
Despite the significance of N-methyladenosine (mA) in gene regulation, the requirement for large amounts of RNA has hindered mA profiling in mammalian early embryos. Here we apply low-input methyl RNA immunoprecipitation and sequencing to map mA in mouse oocytes and preimplantation embryos. We define the landscape of mA during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by mA. In contrast to mA-marked zygotic ally-activated genes, mA-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by mA. Our results provide a foundation for future studies exploring the regulatory roles of mA in mammalian early embryonic development.
尽管 N6-甲基腺苷(m6A)在基因调控中具有重要意义,但由于需要大量的 RNA,m6A 在哺乳动物早期胚胎中的分析一直受到阻碍。在这里,我们应用低输入甲基 RNA 免疫沉淀和测序技术来绘制小鼠卵母细胞和着床前胚胎中的 m6A 图谱。我们定义了母源到合子过渡过程中 m6A 的图谱,包括对细胞命运决定至关重要的特定阶段表达的转录因子。在受精后被降解的母体遗传转录本和在合子基因组激活过程中被激活的合子基因都被广泛地标记为 m6A。与 m6A 标记的合子激活基因不同,m6A 标记的母体遗传转录本更容易被 microRNAs 靶向。此外,来自逆转座子的 RNA,如母系表达的 MTA 和在二细胞阶段转录激活的 MERVL,都被大量地标记为 m6A。我们的研究结果为未来研究 m6A 在哺乳动物早期胚胎发育中的调控作用提供了基础。