Rbm24a dictates mRNA recruitment for germ granule assembly in zebrafish

• Published in: The EMBO journal Vol. 44; no. 11; pp. 3121 - 3149
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.06.2025; EMBO Press
• Subjects: Animals; Biochemistry, Molecular Biology; Biomedical and Life Sciences; Cytoplasmic Granules - metabolism; Development Biology; EMBO11; EMBO36; Genomics; Germ Cells - metabolism; Life Sciences; Ribonucleoproteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; RNA Recruitment; Degron; Ribonucleoprotein Granule; Primordial Germ Cell; Rbm24; Degron Subject Categories Development; RNA Biology
• ISSN: 1460-2075; 0261-4189; 1460-2075
• 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. Synopsis Germ plasm granules are ribonucleoprotein condensates that determine the fate of primordial germ cells (PGCs). This study shows that the maternal RNA binding protein Rbm24a, in complex with Buc, is essential for PGC formation via regulation of germ plasm mRNA recruitment and a directed transport of germ granules. The Rbm24a-Buc complex functions as an organizer for germ granule assembly. Rbm24a alone is sufficient for the recruitment of all known germ plasm mRNAs. Kinesin-1-mediated transport of germ granules to cleavage furrows requires Rbm24a. Targeted Rbm24a protein degradation after cleavage stage prevents PGC formation. Loss of maternal Rbm24a causes a complete degradation of the germ granules and the disappearance of primordial germ cells.