Disordered DBHS Regions Drive Droplet Formation

Stable folded 3D structures of proteins are well characterised and can be confidently predicted in most cases. A large proportion of proteins, however, contain regions enriched in a few amino acids – low-complexity regions (LCRs) – which are often intrinsically disordered. How LCR composition relates to protein behaviour and function is poorly understood. DBHS proteins are abundant multifunctional RNA-binding proteins with a conserved core folded domain flanked on either side by long highly diverse LCRs, providing a unique opportunity for describing LCR composition-function relationships. We show that LCRs allow these proteins to reversibly condense to form liquid droplets, driving dynamic and reversible organisation of molecules in the cell nucleus.