Zhang Yizhuang, Wang Jiasheng, Fang Hailing, Hu Shuqi, Yang Boya, Zhou Jiayi, Grifone Raphaëlle, Li Panfeng, Lu Tong, Wang Zhengyang, Zhang Chong, Huang Yubin, Wu Dalei, Gong Qianqian, Shi De-Li, Li Ang, Shao Ming
Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences and Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 266237, Qingdao, China.
Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, 266237, Qingdao, China.
EMBO J. 2025 Apr 25. doi: 10.1038/s44318-025-00442-z.
The germ granules are ribonucleoprotein (RNP) biomolecular condensates that determine the fate of primordial germ cells (PGCs) and serve as a model for studying RNP granule assembly. Here, we show that the maternal RNA-binding protein Rbm24a is a key factor governing the specific sorting of mRNAs into germ granules. Mechanistically, Rbm24a interacts with the germ plasm component Buc to dictate the specific recruitment of germ plasm mRNAs into phase-separated condensates. Germ plasm particles lacking Rbm24a and mRNAs fail to undergo kinesin-dependent transport toward cleavage furrows where small granules fuse into large aggregates. Therefore, the loss of maternal Rbm24a causes a complete degradation of the germ plasm and the disappearance of PGCs. These findings demonstrate that the Rbm24a/Buc complex functions as a nucleating organizer of germ granules, highlighting an emerging mechanism for RNA-binding proteins in reading and recruiting RNA components into a phase-separated protein scaffold.
生殖颗粒是核糖核蛋白（RNP）生物分子凝聚物，决定原始生殖细胞（PGC）的命运，并作为研究RNP颗粒组装的模型。在这里，我们表明母体RNA结合蛋白Rbm24a是控制mRNA特异性分选到生殖颗粒中的关键因素。从机制上讲，Rbm24a与生殖质成分Buc相互作用，以决定生殖质mRNA特异性募集到相分离的凝聚物中。缺乏Rbm24a和mRNA的生殖质颗粒无法进行驱动蛋白依赖性向分裂沟的运输，在分裂沟处小颗粒融合成大聚集体。因此，母体Rbm24a的缺失导致生殖质完全降解和PGC消失。这些发现表明，Rbm24a/Buc复合物作为生殖颗粒的成核组织者发挥作用，突出了RNA结合蛋白在读取和募集RNA成分到相分离的蛋白质支架中的新出现机制。
