RNA结合蛋白DND1和NANOS3协同抑制生殖细胞谱系的进入。
RNA-binding proteins DND1 and NANOS3 cooperatively suppress the entry of germ cell lineage.
作者信息
Wang Ziqi, Yu Honglin, Gu Zhaoyu, Shi Xiaohui, Ma Jiayue, Shao Qizhe, Yao Yao, Yao Shuo, Xu Yan, Gu Yashi, Dai Jiayue, Liu Qi, Shi Jingyan, Qi Rujie, Jin Yue, Liu Yuqian, Shen Xinchen, Huang Wenwen, Liu Heng-Jia, Jin Min, Liu Wanlu, Brook Matthew, Chen Di
机构信息
Center for Reproductive Medicine of The Second Affiliated Hospital, Center for Regeneration and Cell Therapy of Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Haining, Zhejiang, China.
Edinburgh Medical School: Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK.
出版信息
Nat Commun. 2025 May 23;16(1):4792. doi: 10.1038/s41467-025-57490-6.
Specification of primordial germ cells (PGCs) establishes germline development during early embryogenesis, yet the underlying mechanisms in humans remain largely unknown. Here, we reveal the functional roles of germline-specific RNA-binding protein (RBP) DND1 in human PGC (hPGC) specification. We discovered that DND1 forms a complex with another RBP, NANOS3, to restrict hPGC specification. Furthermore, by analyzing the mRNAs bound by DND1 and NANOS3, we found that DND1 facilitates the binding of NANOS3 to hPGC-like cells-related mRNAs. We identified SOX4 mRNAs as the key downstream factor for the DND1 and NANOS3 complex. Mechanistically, DND1 and NANOS3 function in processing bodies (P-bodies) to repress the translation of SOX4 mRNAs, with NANOS3 mediating the interaction between DND1 and the translational repressor 4E-T. Altogether, these findings identify the RBP complex formed by DND1 and NANOS3 functioning as a "braking system" to restrict the entry of germ cell fate in humans.
原始生殖细胞（PGC）的特化在早期胚胎发育过程中确立了生殖系的发育，但人类中潜在的机制仍 largely 未知。在这里，我们揭示了生殖系特异性 RNA 结合蛋白（RBP）DND1 在人类 PGC（hPGC）特化中的功能作用。我们发现 DND1 与另一种 RBP，NANOS3 形成复合物以限制 hPGC 特化。此外，通过分析与 DND1 和 NANOS3 结合的 mRNA，我们发现 DND1 促进 NANOS3 与 hPGC 样细胞相关 mRNA 的结合。我们将 SOX4 mRNA 鉴定为 DND1 和 NANOS3 复合物的关键下游因子。从机制上讲，DND1 和 NANOS3 在加工小体（P 小体）中发挥作用以抑制 SOX4 mRNA 的翻译，其中 NANOS3 介导 DND1 与翻译抑制因子 4E-T 之间的相互作用。总之，这些发现确定了由 DND1 和 NANOS3 形成的 RBP 复合物作为一种“制动系统”来限制人类生殖细胞命运的进入。
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