LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs

DOI Web Site 被引用文献1件
  • Jun-Yan Kang
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Ze Wen
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Duo Pan
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Yuhan Zhang
    Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai Research Center of Biliary Tract Disease, Department of General Surgery, Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Qing Li
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Ai Zhong
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Xinghai Yu
    State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
  • Yi-Chen Wu
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Yu Chen
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Xiangzheng Zhang
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Peng-Cheng Kou
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Junlan Geng
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Ying-Yi Wang
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Min-Min Hua
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Ruiting Zong
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Biao Li
    Department of Nuclear Medicine, Rui Jin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
  • Hui-Juan Shi
    NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Pharmacy School, Fudan University, Shanghai, China.
  • Dangsheng Li
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Xiang-Dong Fu
    Department of Cellular and Molecular Medicine, University of California, San Diego, CA, USA.
  • Jinsong Li
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • David L. Nelson
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Xuejiang Guo
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Yu Zhou
    State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
  • Lan-Tao Gou
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Ying Huang
    Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai Research Center of Biliary Tract Disease, Department of General Surgery, Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Mo-Fang Liu
    State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

抄録

<jats:p> Postmeiotic spermatids use a unique strategy to coordinate gene expression with morphological transformation, in which transcription and translation take place at separate developmental stages, but how mRNAs stored as translationally inert messenger ribonucleoproteins in developing spermatids become activated remains largely unknown. Here, we report that the RNA binding protein FXR1, a member of the fragile X–related (FXR) family, is highly expressed in late spermatids and undergoes liquid-liquid phase separation (LLPS) to merge messenger ribonucleoprotein granules with the translation machinery to convert stored mRNAs into a translationally activated state. Germline-specific <jats:italic>Fxr1</jats:italic> ablation in mice impaired the translation of target mRNAs and caused defective spermatid development and male infertility, and a phase separation–deficient FXR1 <jats:sup>L351P</jats:sup> mutation in <jats:italic>Fxr1</jats:italic> knock-in mice produced the same developmental defect. These findings uncover a mechanism for translational reprogramming with LLPS as a key driver in spermiogenesis. </jats:p>

収録刊行物

  • Science

    Science 377 (6607), eabj6647-, 2022-08-12

    American Association for the Advancement of Science (AAAS)

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