Rbm24 dictates mRNA recruitment for germ plasm assembly

Ribonucleoprotein (RNP) granules are the most common membrane-less biomolecular condensates. However, the mechanisms underlying their assembly are largely unknown. The aggregation of germ plasm determines the fate of primordial germ cells (PGCs) and serves as a model for RNP granule assembly. Here, we show that maternal RNA binding protein Rbm24a is the key factor governing specific sorting of mRNAs. Mechanistically, Rbm24a complexes with Buc and interacts to dictate the specific grasp of germ plasm mRNAs into phase-separated condensates. Germ plasm particles lacking Rbm24a and mRNAs fail to undergo kinesin-dependent transport towards the cleavage furrows where small granules fuse into large aggregates. Therefore, the loss of maternal Rbm24a causes a complete degradation of germ plasm and the disappearance of PGCs. These findings demonstrate that Rbm24a functions as a nucleating organizer of the germ plasm, highlighting an emerging mechanism for RNA-binding proteins in reading and recruiting RNA components into the phase-separated protein scaffold. Overall design: To examine the global transcriptome alterations following the loss of maternal Rbm24a, we conducted bulk RNA-seq analysis on Mrbm24a and their sibling embyos at 4-cell, sphere stage and 24 hpf.

核糖核蛋白（Ribonucleoprotein, RNP）颗粒是最为常见的无膜生物分子凝聚体，但其组装背后的分子机制目前仍未被完全阐明。生殖质的聚集决定了原始生殖细胞（Primordial Germ Cells, PGCs）的命运，同时也可作为RNP颗粒组装的经典研究模型。本研究发现，母源RNA结合蛋白Rbm24a是调控mRNA特异性分选的关键因子。从机制层面来看，Rbm24a与Buc形成复合物并发生相互作用，进而介导生殖质mRNA被特异性捕获并进入相分离凝聚体的过程。缺乏Rbm24a与mRNA的生殖质颗粒无法完成依赖驱动蛋白的运输，无法抵达小颗粒融合形成大聚集体的卵裂沟区域。因此，母源Rbm24a的缺失会导致生殖质完全降解，并引发原始生殖细胞的消失。上述研究结果证实，Rbm24a可作为生殖质的成核组织者，揭示了RNA结合蛋白通过识别并招募RNA组分进入相分离蛋白支架的新型调控机制。整体实验设计：为探究母源Rbm24a缺失后全球转录组的变化情况，我们分别对4细胞期、囊胚期以及受精后24小时（hours post fertilization, hpf）的M rbm24a突变胚胎及其同窝对照胚胎开展了批量RNA测序（bulk RNA-seq）分析。