Abstract: Embryonic development relies on post-transcriptional regulatory networks, with RNA-binding proteins (RBPs) playing key roles. Among these, PUMILIO (PUM) proteins are essential for early embryogenesis. Mice lacking both PUM1 and PUM2 fail to undergo gastrulation and exhibit embryonic lethality, yet their precise regulatory mechanisms remain unclear. Using embryoid bodies (EBs) as an in vitro model of early embryogenesis, we show that PUM1 and PUM2 coordinate germline suppression, pluripotency regulation, and somatic differentiation to maintain lineage balance. PUM proteins directly repress Prdm1 to prevent premature germline specification while promoting somatic differentiation by modulating pluripotency networks and Wnt signaling. Their loss disrupts germ layer differentiation, impairs anterior-posterior (A-P) and dorsoventral (D-V) patterning, and leads to defective neural differentiation. RIP-seq analyses reveal that PUM1 and PUM2 directly regulate mRNAs associated with these developmental processes, defining a post-transcriptional network that integrates RNA regulation with developmental signaling. These findings establish PUM proteins as essential post-transcriptional regulators of early embryogenesis, demonstrating how RBPs coordinate cell fate and patterning.
Funding Source: Start-up funding for research groups at ShanghaiTech University
