METTL3 catalyzes the formation of N⁶-methyl-adenosine (m⁶A) 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 m⁶A 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 m⁶A modification in spermatogenesis and reproduction in mammals.

中文翻译：

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Mettl3 介导的 m6A 调节精原细胞分化和减数分裂起始。

METTL3 催化 N ⁶ -甲基腺苷 (m ⁶ A)的形成，其在调节各种生物过程中具有重要作用。然而，Mettl3 的体内功能在哺乳动物中仍然未知。在这里，我们生成了生殖细胞特异性 Mettl3 基因敲除小鼠，并证明 Mettl3 对男性生育能力和精子发生至关重要。生殖细胞中 Mettl3 的消融严重抑制了精原细胞分化并阻止了减数分裂的开始。转录组和 m ⁶谱分析显示在精子发生中起作用的基因改变了表达谱和选择性剪接。我们的发现为 Mettl3 介导的 m ⁶的功能和调节机制提供了新的见解哺乳动物精子发生和繁殖的改变。