LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs.

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 Fxr1 ablation in mice impaired the translation of target mRNAs and caused defective spermatid development and male infertility, and a phase separation-deficient FXR1L351P mutation in Fxr1 knock-in mice produced the same developmental defect. These findings uncover a mechanism for translational reprogramming with LLPS as a key driver in spermiogenesis.

Citation

Jun-Yan Kang, Ze Wen, Duo Pan, Yuhan Zhang, Qing Li, Ai Zhong, Xinghai Yu, Yi-Chen Wu, Yu Chen, Xiangzheng Zhang, Peng-Cheng Kou, Junlan Geng, Ying-Yi Wang, Min-Min Hua, Ruiting Zong, Biao Li, Hui-Juan Shi, Dangsheng Li, Xiang-Dong Fu, Jinsong Li, David L Nelson, Xuejiang Guo, Yu Zhou, Lan-Tao Gou, Ying Huang, Mo-Fang Liu. LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs. Science (New York, N.Y.). 2022 Aug 12;377(6607):eabj6647

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PMID: 35951695

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