Abstract 1029 Gain-of-function RNA Polymerase II partitioning is a shared feature of diverse oncogenic fusion condensates

Condensates regulate transcription by selectively compartmentalizing biomolecules, yet the rules of specificity and their relationship to function remain enigmatic. To identify rules linked to function, we leverage the genetic selection bias of condensate-promoting oncofusions. Focusing on the three most frequent oncofusions driving translocation renal cell carcinoma, we find that they promote the formation of condensates that activate transcription by gain-of-function RNA Polymerase II partitioning through a shared signature of elevated p and p-interacting residues and depletion of aliphatic residues.