RNA-binding proteins DND1 and NANOS3 cooperatively suppress the entry of germ cell lineage
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.
Authors
- Jingbo Dai (ORCID: https://orcid.org/0000-0001-7562-9039)
- Matthew Brook (ORCID: https://orcid.org/0000-0003-1245-7385)
- Qizhe Shao (ORCID: https://orcid.org/0009-0001-8572-7019)
- Yao Yao (ORCID: https://orcid.org/0000-0001-8020-9696)
- J. Ma (ORCID: https://orcid.org/0009-0007-8120-7810)
- Xiaohui Shi (ORCID: https://orcid.org/0000-0001-5610-9775)
- Min Jin (ORCID: https://orcid.org/0000-0002-1390-4549)
- Heng-Jia Liu (ORCID: https://orcid.org/0000-0001-9685-6572)
- Xinchen Shen (ORCID: https://orcid.org/0009-0001-7053-1240)
- Yue Jin (ORCID: https://orcid.org/0000-0002-4220-5018)
- Di Chen (ORCID: https://orcid.org/0000-0002-9451-9721)
- Wenwen Huang (ORCID: https://orcid.org/0000-0001-8175-9083)
- Yuqian Liu (ORCID: https://orcid.org/0000-0001-8536-0854)
- Ziqi Wang (ORCID: https://orcid.org/0009-0007-6701-5177)
- Qi Liu (ORCID: https://orcid.org/0000-0003-2106-7231)
- Jingyan Shi
- Honglin Yu
- Yan Xu (ORCID: https://orcid.org/0009-0005-8274-8681)
- Wanlu Liu (ORCID: https://orcid.org/0000-0001-5963-2908)
- Zhaoyu Gu (ORCID: https://orcid.org/0000-0003-2277-3998)
- Yashi Gu
- Ruixuan Qi
Institutions
- Edinburgh College (GB)
- Guangxi Transportation Research Institute (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Zhejiang University-University of Edinburgh Institute (CN)
- The Queen's Medical Research Institute (GB)
- Alibaba Group (China) (CN)
- Zhejiang University (CN)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-23
- DOI
- https://doi.org/10.1038/s41467-025-57490-6
- Citations
- 7
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- National Natural Science Foundation of China
- Zhejiang University
- Natural Science Foundation of Zhejiang Province