Intrinsically disordered regions: a platform for regulated assembly of biomolecular condensates

Intrinsically disordered regions (IDRs) readily phase-separate in vitro and are often assumed to drive the formation of biomolecular condensates in cells. In this chapter, we review genetic experiments that have defined protein scaffolds, and the domains wherein, that support the assembly of P-bodies, germ granules, stress granules, and other condensates that form in the cytoplasm. Typical scaffolds are multivalent proteins that use structured domains to mediate the protein–protein or protein–RNA interactions that drive phase separation. IDRs are rarely sufficient, and often not even necessary, to drive condensate assembly in cells. Rather, IDRs play regulatory roles, linking phase separation to environmental inputs and modifying the material properties of condensates. The conformational flexibility of IDRs makes them ideal “sensors” in the cellular context and provides a platform for regulated assembly of biomolecular condensates.