State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China.
Department of Biotechnology, Beijing Institude of Radiation Medicine, Beijing, China.
Cell Cycle. 2020 Feb;19(4):391-404. doi: 10.1080/15384101.2019.1711324. Epub 2020 Jan 9.
N-methyladenosine (mA) is the most prevalent epigenetic modification of messenger RNA (mRNA) in higher eukaryotes; this modification is mainly catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. Although mA modification has been proven to play an essential role in diverse biological processes, our knowledge of is still limited because mutations are lethal to embryos in both mammals and plants. In this study, we knocked down by microinjection of its specific short interfering RNAs (siRNAs) or morpholino into fully grown germinal vesicle (GV) oocytes. As a result, we demonstrated that knocking down in female germ cells severely inhibited oocyte maturation by decreasing mRNA translation efficiency and led to defects in the maternal-to-zygotic transition, probably due to its interference in disrupting mRNA degradation. The discovery from this study suggests that the reversible mA modification has vital functions in mammalian oocyte maturation and pre-implantation embryonic development processes.
N6-甲基腺苷（m6A）是真核生物中信使 RNA（mRNA）最普遍的表观遗传修饰；这种修饰主要由甲基转移酶复合物催化，其中甲基转移酶样蛋白 3（METTL3）是关键因素。尽管 m6A 修饰已被证明在多种生物过程中发挥着重要作用，但由于其突变在哺乳动物和植物中对胚胎都是致命的，我们对其的了解仍然有限。在这项研究中，我们通过将其特异性短发夹 RNA（siRNA）或吗啉代寡核苷酸显微注射到完全生长的生发泡（GV）卵母细胞中，敲低了 METTL3。结果表明，敲低雌性生殖细胞中的 METTL3 通过降低 mRNA 翻译效率严重抑制卵母细胞成熟，并导致母源到合子过渡的缺陷，这可能是由于其干扰了 mRNA 的降解。这项研究的发现表明，可逆的 m6A 修饰在哺乳动物卵母细胞成熟和植入前胚胎发育过程中具有重要功能。
