LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- Xinghai Yu
- State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
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- 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.
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- Yu Chen
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
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- Xiangzheng Zhang
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
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- 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.
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- 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.
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- 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.
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- 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.
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- Ruiting Zong
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
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- Biao Li
- Department of Nuclear Medicine, Rui Jin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
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- Hui-Juan Shi
- NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Pharmacy School, Fudan University, Shanghai, China.
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- 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.
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- Xiang-Dong Fu
- Department of Cellular and Molecular Medicine, University of California, San Diego, CA, USA.
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- 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.
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- David L. Nelson
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
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- Xuejiang Guo
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
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- Yu Zhou
- State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
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- 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.
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- 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.
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- 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.
Description
<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>
Journal
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- Science
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Science 377 (6607), eabj6647-, 2022-08-12
American Association for the Advancement of Science (AAAS)
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Details 詳細情報について
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- CRID
- 1360298761827413504
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- ISSN
- 10959203
- 00368075
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- Data Source
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- Crossref