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

First Author  Kang JY Year  2022
Journal  Science Volume  377
Issue  6607 Pages  eabj6647
PubMed ID  35951695 Mgi Jnum  J:332641
Mgi Id  MGI:7330283 Doi  10.1126/science.abj6647
Citation  Kang JY, et al. (2022) LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs. Science 377(6607):eabj6647
abstractText  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 FXR1(L351P) 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.
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