Preprint Highlight: Cytoplasmic forces functionally reorganize nuclear condensates in oocytes.

Abstract

Cytoskeletal motor-based cytoplasmic remodeling in mammalian oocytes is critical for proper oocyte development. Nevertheless, the function, spatiotemporal regulation, and evolutionary conservation of this remodeling remain unclear. This study tests the hypothesis that cytoplasmic forces drive coalescence of nuclear liquid condensates involved in RNA processing. Simulations, live imaging, drug treatments, and genetic experiments in mouse oocytes demonstrate that cytoplasmic forces drive condensate-associated mRNA splicing. Importantly, this splicing is essential for meiotic cell divisions and fertility. Additional experiments in Drosophila oocytes demonstrate that cytoplasmic forces play a conserved role in meiosis. These data imply that cytoskeletal force generation and nuclear condensate dynamics play an evolutionarily conserved function in a broad array of cell types and processes. This work has important implications for human fertility and condensate-linked diseases including neurodegeneration and cancer.