Whitehead Institute, Cambridge, United States.
Reproductive Medicine Center, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Elife. 2020 Jul 20;9:e56523. doi: 10.7554/eLife.56523.
Fertility across metazoa requires the germline-specific DAZ family of RNA-binding proteins. Here we examine whether DAZL directly regulates progenitor spermatogonia using a conditional genetic mouse model and in vivo biochemical approaches combined with chemical synchronization of spermatogenesis. We find that the absence of impairs both expansion and differentiation of the spermatogonial progenitor population. In undifferentiated spermatogonia, DAZL binds the 3' UTRs of ~2,500 protein-coding genes. Some targets are known regulators of spermatogonial proliferation and differentiation while others are broadly expressed, dosage-sensitive factors that control transcription and RNA metabolism. DAZL binds 3' UTR sites conserved across vertebrates at a UGUU(U/A) motif. By assessing ribosome occupancy in undifferentiated spermatogonia, we find that DAZL increases translation of its targets. In total, DAZL orchestrates a broad translational program that amplifies protein levels of key spermatogonial and gene regulatory factors to promote the expansion and differentiation of progenitor spermatogonia.
跨后生动物的生殖能力需要生殖系特异性的 DAZ 家族 RNA 结合蛋白。在这里，我们使用条件性遗传小鼠模型和体内生化方法以及生精作用的化学同步化，研究了 DAZL 是否直接调节祖细胞精原细胞。我们发现缺失会损害精原细胞祖细胞群体的扩增和分化。在未分化的精原细胞中，DAZL 结合了约 2500 个编码蛋白质的基因的 3'UTR。一些靶标是已知的精原细胞增殖和分化的调节因子，而其他靶标则是广泛表达的、剂量敏感的因子，它们控制转录和 RNA 代谢。DAZL 在 UGUU（U/A）基序处结合了跨脊椎动物保守的 3'UTR 位点。通过评估未分化精原细胞中的核糖体占据情况，我们发现 DAZL 增加了其靶标的翻译。总的来说，DAZL 协调了一个广泛的翻译程序，该程序扩增了关键精原细胞和基因调节因子的蛋白质水平，以促进祖细胞精原细胞的扩增和分化。
