State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Cell Res. 2017 Sep;27(9):1100-1114. doi: 10.1038/cr.2017.100. Epub 2017 Aug 15.
METTL3 catalyzes the formation of N-methyl-adenosine (mA) which has important roles in regulating various biological processes. However, the in vivo function of Mettl3 remains largely unknown in mammals. Here we generated germ cell-specific Mettl3 knockout mice and demonstrated that Mettl3 was essential for male fertility and spermatogenesis. The ablation of Mettl3 in germ cells severely inhibited spermatogonial differentiation and blocked the initiation of meiosis. Transcriptome and mA profiling analysis revealed that genes functioning in spermatogenesis had altered profiles of expression and alternative splicing. Our findings provide novel insights into the function and regulatory mechanisms of Mettl3-mediated mA modification in spermatogenesis and reproduction in mammals.
METTL3 催化 N6-甲基腺苷（m6A）的形成，m6A 在调节各种生物过程中具有重要作用。然而，Mettl3 在哺乳动物体内的功能在很大程度上尚不清楚。在这里，我们生成了生殖细胞特异性的 Mettl3 敲除小鼠，并证实 Mettl3 对于雄性生育力和精子发生是必需的。生殖细胞中 Mettl3 的缺失严重抑制了精原细胞的分化，并阻断了减数分裂的起始。转录组和 m6A 谱分析显示，在精子发生中起作用的基因的表达和选择性剪接发生了改变。我们的研究结果为 Mettl3 介导的 m6A 修饰在哺乳动物精子发生和生殖中的功能和调控机制提供了新的见解。
