Mouse oocytes organize mRNA-protein assemblies and ER-associated translation hubs to drive meiosis

Abstract

Oocyte meiosis in animals is essential for producing fertilizable eggs. As transcription becomes largely quiescent, meiotic progression depends on temporally regulated translation of accumulated maternal mRNAs. However, the underlying mechanisms remain unclear. Here, we identified diverse and highly organized mRNA-protein assemblies in mouse oocytes that coordinate cytoplasmic mRNA regulation and enable spatiotemporal translation to drive oocyte meiosis. Twelve RNA-binding proteins (RBPs), including DDX4/VASA, HDLBP/Vigilin, and TDRD3, were assembled into widely distributed aggregates in germinal vesicle (GV)-stage oocytes. We depleted DDX4 and HDLBP using Trim-Away and found that these RBPs regulate the precise assembly of RNA granules and protein aggregates through distinct mechanisms, promoting temporal protein synthesis at cortical translation factories with the endoplasmic reticulum, termed CORTE. All 12 RBPs formed distinct mRNA-protein assemblies, whose size and distribution changed upon meiotic initiation. These findings reveal the molecular basis of spatiotemporal mRNA-protein-organelle networks underlying animal reproduction and development.