The role of a hidden ordered domain in controlling the material properties of RNA-protein condensates

Biomolecular condensates are a diverse class of membraneless, intracellular bodies that organize biochemistry. The constituent molecules, often RNA and protein, phase separate from a soluble pool into condensates which are crucial for normal physiological function but are also implicated in the development of several neurological diseases. Condensates can range from liquid-like droplets to solid-like aggregates. However, the distribution of condensate material properties along the viscoelastic continuum has not been well characterized, the molecular basis is poorly understood, and the corresponding functional consequences for cells are largely unknown. We have identified a coiled-coil (CC) motif within the disordered polyQ tract of a phase separating protein that strongly influences the material states of resulting RNA-protein condensates. By mutating specific residues in the CC, we demonstrate a range of material states in vitro, characterized by kinetic mean-field modeling of condensate formation. The CC domain structure is predicted by atomistic monte carlo simulations which are complemented by circular dichroism. Finally, integration of CC mutants into cells provides an in vivo system that demonstrates a link between the material state of condensates and cell function.