Molecular control of ribonucleoprotein granule disassembly during mitosis centers on signals that reduce multivalent interactions holding condensates together and on changes in cellular compartmentalization that alter RNA and protein availability. Work on biomolecular phase separation by Clifford Brangwynne at Princeton University and Anthony Hyman at Max Planck Institute of Molecular Cell Biology and Genetics established the physical basis for condensate assembly and showed how regulated dissolution can control developmental cell divisions, providing a framework for mitotic granule disassembly.
Kinases and post-translational modifications
A primary mechanism is regulated phosphorylation of scaffold and RNA-binding proteins by mitotic kinases. Cyclin-dependent kinase 1 (CDK1) activity at mitotic entry, together with Polo-like kinase 1 (PLK1) and Aurora kinases, modifies low-complexity and intrinsically disordered domains to weaken multivalent contacts and shift proteins toward a more soluble state. The dual-specificity kinase DYRK3 has been implicated as a mitosis-associated regulator that promotes dissolution of stress granules and other condensates, acting as a seasonal “solubilizer” during mitosis. These phosphorylation events are often combinatorial and context-dependent, so different granule types respond differently in timing and extent of disassembly.
Transport, RNA availability and proteostasis
Mitotic nuclear envelope breakdown reorganizes nucleocytoplasmic partitioning and alters the local concentration of RNAs and nuclear transport factors, which changes the valency driving granule stability. Changes in mRNA translation and decay during mitosis reduce the RNA scaffolds that sustain many ribonucleoprotein granules. Molecular chaperones and the ubiquitin–proteasome system contribute to clearance and remodeling: chaperones can actively dissolve aberrant assemblies, while targeted ubiquitination can mark persistent components for degradation. Paul Anderson at Brigham and Women’s Hospital has characterized stress granule components and signaling pathways that intersect with these proteostatic systems.
Misregulation of these signals has biological and clinical consequences. Proper, timely disassembly supports accurate chromosome segregation and cell-cycle progression and is important in developmental contexts such as germline condensate remodeling described by Brangwynne and Hyman. Failure to dissolve RNP granules or inappropriate persistence of solidified assemblies is linked to neurodegenerative disease and impaired stress responses, an outcome that highlights the intersection of cell-cycle control, protein chemistry, and organismal health. Ongoing work aims to map kinase–substrate networks and the interplay with RNA metabolism to predict when and how granules dissolve across species and tissues.