N⁶-methyladenosine (m⁶A) is the most common internal modification in eukaryotic mRNA. It is dynamically installed and removed, and acts as a new layer of mRNA metabolism, regulating biological processes including stem cell pluripotency, cell differentiation, and energy homeostasis. m⁶A is recognized by selective binding proteins; YTHDF1 and YTHDF3 work in concert to affect the translation of m⁶A-containing mRNAs, YTHDF2 expedites mRNA decay, and YTHDC1 affects the nuclear processing of its targets. The biological function of YTHDC2, the final member of the YTH protein family, remains unknown. We report that YTHDC2 selectively binds m⁶A at its consensus motif. YTHDC2 enhances the translation efficiency of its targets and also decreases their mRNA abundance. Ythdc2 knockout mice are infertile; males have significantly smaller testes and females have significantly smaller ovaries compared to those of littermates. The germ cells of Ythdc2 knockout mice do not develop past the zygotene stage and accordingly, Ythdc2 is upregulated in the testes as meiosis begins. Thus, YTHDC2 is an m⁶A-binding protein that plays critical roles during spermatogenesis.

中文翻译：

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Ythdc2 是一种 N6-甲基腺苷结合蛋白，可调节哺乳动物精子发生。

N ⁶ -甲基腺苷 (m ⁶ A) 是真核 mRNA 中最常见的内部修饰。它是动态安装和移除的，作为 mRNA 代谢的新层，调节生物过程，包括干细胞多能性、细胞分化和能量稳态。m ⁶ A 被选择性结合蛋白识别；YTHDF1 和 YTHDF3 协同作用影响含m ⁶ A 的 mRNA的翻译，YTHDF2 加速 mRNA 衰变，而 YTHDC1 影响其靶标的核加工。YTHC2 是 YTH 蛋白家族的最后一个成员，其生物学功能仍然未知。我们报告 YTHDC2 选择性地结合 m ⁶A 在其共识主题。YTHDC2 提高了其靶标的翻译效率并降低了其 mRNA 丰度。Ythdc2 基因敲除小鼠不育；与同窝出生的动物相比，雄性的睾丸要小得多，而雌性的卵巢要小得多。Ythdc2 敲除小鼠的生殖细胞不会发育超过合子期，因此，随着减数分裂开始，Ythdc2 在睾丸中被上调。因此，YTHDC2 是一种 m ⁶ A 结合蛋白，在精子发生过程中起关键作用。