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RNA-binding proteins DND1 and NANOS3 cooperatively suppress the entry of germ cell lineage

Author

Listed:
  • Ziqi Wang

    (Zhejiang University)

  • Honglin Yu

    (Zhejiang University
    The University of Edinburgh)

  • Zhaoyu Gu

    (Zhejiang University)

  • Xiaohui Shi

    (Zhejiang University)

  • Jiayue Ma

    (Zhejiang University)

  • Qizhe Shao

    (Zhejiang University)

  • Yao Yao

    (Zhejiang University)

  • Shuo Yao

    (Zhejiang University)

  • Yan Xu

    (Zhejiang University)

  • Yashi Gu

    (Zhejiang University
    The University of Edinburgh)

  • Jiayue Dai

    (Zhejiang University
    The University of Edinburgh)

  • Qi Liu

    (Zhejiang University)

  • Jingyan Shi

    (Zhejiang University)

  • Rujie Qi

    (Zhejiang University)

  • Yue Jin

    (The University of Edinburgh
    Zhejiang University)

  • Yuqian Liu

    (The University of Edinburgh
    Zhejiang University)

  • Xinchen Shen

    (Zhejiang University)

  • Wenwen Huang

    (Zhejiang University)

  • Heng-Jia Liu

    (The University of Edinburgh
    Zhejiang University)

  • Min Jin

    (Zhejiang University)

  • Wanlu Liu

    (Zhejiang University
    Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Matthew Brook

    (Queen’s Medical Research Institute, University of Edinburgh)

  • Di Chen

    (Zhejiang University
    The University of Edinburgh
    State Key Laboratory of Biobased Transportation Fuel Technology
    Zhejiang University)

Abstract

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.

Suggested Citation

  • Ziqi Wang & Honglin Yu & Zhaoyu Gu & Xiaohui Shi & Jiayue Ma & Qizhe Shao & Yao Yao & Shuo Yao & Yan Xu & Yashi Gu & Jiayue Dai & Qi Liu & Jingyan Shi & Rujie Qi & Yue Jin & Yuqian Liu & Xinchen Shen , 2025. "RNA-binding proteins DND1 and NANOS3 cooperatively suppress the entry of germ cell lineage," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57490-6
    DOI: 10.1038/s41467-025-57490-6
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