YTHDF2 binds and destabilizes N⁶-methyladenosine (m⁶A)-modified mRNA. The extent to which this branch of m⁶A RNA-regulatory pathway functions in vivo and contributes to mammalian development remains unknown. Here we find that YTHDF2 deficiency is partially permissive in mice and results in female-specific infertility. Using conditional mutagenesis, we demonstrate that YTHDF2 is autonomously required within the germline to produce MII oocytes that are competent to sustain early zygotic development. Oocyte maturation is associated with a wave of maternal RNA degradation, and the resulting relative changes to the MII transcriptome are integral to oocyte quality. The loss of YTHDF2 results in the failure to regulate transcript dosage of a cohort of genes during oocyte maturation, with enrichment observed for the YTHDF2-binding consensus and evidence of m⁶A in these upregulated genes. In summary, the m⁶A-reader YTHDF2 is an intrinsic determinant of mammalian oocyte competence and early zygotic development.

YTHDF2 结合 N ⁶ -甲基腺苷 (m ⁶ A) 修饰的 mRNA 并使其不稳定。^{m 6} A RNA 调节途径的这一分支在体内发挥作用以及对哺乳动物发育的贡献程度仍不清楚。在这里，我们发现 YTHDF2 缺陷在小鼠中是部分允许的，并导致女性特有的不孕症。通过条件诱变，我们证明了种系内自主需要 YTHDF2 来产生能够维持早期合子发育的 MII 卵母细胞。卵母细胞成熟与母体 RNA 降解波相关，由此产生的 MII 转录组的相对变化是卵母细胞质量不可或缺的一部分。YTHDF2 的缺失导致在卵母细胞成熟过程中无法调节一组基因的转录剂量，观察到 YTHDF2 结合共识的富集和这些上调基因中m ^{6 A 的证据。}总之，m ⁶ A 阅读器 YTHDF2 是哺乳动物卵母细胞能力和早期合子发育的内在决定因素。