RNA-binding proteins (RBPs), as key regulators of mRNA fate, are abundantly expressed in the testis. However, RBPs associated with human male infertility remain largely unknown. Through bioinformatic analyses, we identified 62 such RBPs, including an evolutionarily conserved RBP, DEAD-box helicase 20 (DDX20). Male germ-cell-specific inactivation of Ddx20 at E15.5 caused T1-propsermatogonia (T1-ProSG) to fail to reenter cell cycle during the first week of testicular development in mice. Consequently, neither the foundational spermatogonial stem cell (SSC) pool nor progenitor spermatogonia were ever formed in the knockout testes. Mechanistically, DDX20 functions to control the translation of its target mRNAs, many of which encode cell-cycle-related regulators, by interacting with key components of the translational machinery in prospermatogonia. Our data demonstrate a previously unreported function of DDX20 as a translational regulator of critical cell-cycle-related genes, which is essential for cell-cycle reentry of T1-ProSG and formation of the SSC pool.

RNA 结合蛋白 (RBP) 作为 mRNA 命运的关键调节因子，在睾丸中大量表达。然而，RBP 与人类男性不育症的相关性仍然很大程度上未知。通过生物信息学分析，我们鉴定了 62 个这样的 RBP，包括进化上保守的 RBP，DEAD-box 解旋酶 20 (DDX20)。雄性生殖细胞在 E15.5 处特异性失活Ddx20导致 T1-Prosermatogonia (T1-ProSG) 在小鼠睾丸发育的第一周内无法重新进入细胞周期。因此，在基因敲除的睾丸中，基础精原干细胞（SSC）池和祖精原细胞都没有形成。从机制上讲，DDX20 通过与精原细胞中翻译机制的关键组件相互作用来控制其靶标 mRNA 的翻译，其中许多靶标 mRNA 编码细胞周期相关调节因子。我们的数据证明了 DDX20 作为关键细胞周期相关基因的翻译调节因子的先前未报道的功能，这对于 T1-ProSG 的细胞周期重入和 SSC 库的形成至关重要。