Cytoplasmic forces functionally reorganize nuclear condensates in oocytes

Cells remodel their cytoplasm with force-generating cytoskeletal motors1. Their activity generates random forces that stir the cytoplasm, agitating and displacing membrane-bound organelles like the nucleus in somatic2-4 and germ5-7 cells. These forces are transmitted inside the nucleus4,7, yet their consequences on liquid-like biomolecular condensates8-10 residing in the nucleus remain unexplored. Here, we probe experimentally and computationally diverse nuclear condensates, that include splicing speckles, Cajal bodies, and nucleoli, during cytoplasmic remodeling of female germ cells named oocytes. We discover that growing mammalian oocytes deploy cytoplasmic forces to timely impose multiscale reorganization of condensates inside the nucleus. We determine that cytoplasmic forces accelerate nuclear condensate collision-coalescence and molecular kinetics within condensates. Inversely, disrupting the forces decelerates nuclear condensate reorganization on both scales. We link the molecular deceleration found in mRNA-processing splicing speckles to reduced and altered splicing of mRNA, which in oocytes impedes fertility11. We establish that different sources of cytoplasmic forces can reorganize nuclear condensates and that this cytoplasmic aptitude for subnuclear reorganization is evolutionary conserved in insects. Our work implies that cells evolved a mechanism, based on cytoplasmic force tuning, to functionally regulate a broad range of nuclear condensates across scales. This finding opens new perspectives when studying condensate-associated pathologies like cancer, neurodegeneration and viral infections12. One sentence summaryCytoplasmic random forces in growing oocytes drive multiscale reorganization of nuclear liquid-like biomolecular condensates.