Phase-separating RNA-binding proteins form heterogeneous distributions of clusters in subsaturated solutions

Macromolecular phase separation is thought to be one of the processes that drives the formation of membraneless biomolecular condensates in cells. The dynamics of phase separation are thought to follow the tenets of classical nucleation theory, and, therefore, subsaturated solutions should be devoid of clusters with more than a few molecules. We tested this prediction using in vitro biophysical studies to characterize subsaturated solutions of phase-separating RNA-binding proteins with intrinsically disordered prion-like domains and RNA-binding domains. Surprisingly, and in direct contradiction to expectations from classical nucleation theory, we find that subsaturated solutions are characterized by the…

• WT
  Wellcome Trust

  Award: 209194/Z/17/Z
• DF
  Deutsche Forschungsgemeinschaft

  Award: SPP2191
• NI
  National Institutes of Health

  Awards: 5R01NS1056114, R01NS121114