Role of prion-like domains in the transcriptional reprogramming by FET-family oncofusions

Prion-like domains (PLDs) are disordered polypeptides enriched in uncharged polar and aromatic residues.They are synonymous with RNA-binding proteins (RBPs) that aggregate and are associated with neurodegeneration such as FUS, TDP43, and hnRNPA1. At a molecular level, PLDs can drive the liquid-liquid phase separation of the RBPs and their recruitment to specific cellular membrane-less compartments. Interestingly, chromosomal translocations within cells can lead to the formation of fusion proteins where the PLD of an RBP is fused to a DNA-binding domain (DBD).