研究人员报告了RNA结合蛋白FXR1，即脆性X相关（FXR）家族的成员，在晚期精子中高度表达，并进行液-液相分离（LLPS），将信使核糖核酸蛋白颗粒与翻译机器合并，将储存的mRNA转换成翻译活化状态。小鼠的生殖特异性Fxr1敲除损害了靶标mRNA的翻译，导致精子发育缺陷和男性不育，而Fxr1基因敲入小鼠的相分离缺陷FXR1L351P突变也产生了同样的发育缺陷。这些发现揭示了一种以LLPS作为精子发生的关键驱动因素的翻译重编程机制。
据了解，减数分裂后的精子使用一种独特的策略来协调基因表达与形态转化，其中转录和翻译在不同的发育阶段进行，但在发育中的精子中作为翻译惰性信使核糖核酸蛋白储存的mRNA如何被激活，在很大程度上仍是未知数。
附：英文原文
Title: LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs
Author: 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
Issue&Volume: 2022-08-12
Abstract: 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.
DOI: abj6647
Source: https://www.science.org/doi/10.1126/science.abj6647