Intrinsically disordered regions stimulate concentration of small nucleolar ribonucleoproteins and formation of Cajal bodies and nucleoli

One of the densest compartments in the cell is the dense fibrillar component (DFC) of the nucleolus, consisting mainly of nascent ribosomal RNA (rRNA), small nucleolar ribonucleoproteins (snoRNPs), and their chaperone, Nopp140 (gene name NOLC1 ). How this biomolecular condensate is formed and what underlies its structure and function are poorly understood, like those of most liquid–liquid phase-separated condensates. Although we established that Nopp140 is important for the cohesiveness of the DFC and for rRNA modification, it is not known how this is achieved. Here we demonstrate that Nopp140 concentrates intrinsically disordered and nuclear localization signal (NLS)-rich protein regions (IDRs), including a newly identified RNA polymerase I C-terminal domain (CTD) of the RNA polymerase I-associated factor PAF49. Altogether, this network of multivalent weak interactions forms the DFC, a liquid–liquid phase-separated biomolecular condensate that promotes rRNA modification. This local concentration of biomolecules ensures near-complete modification efficiency at some 200 nt in every one of the 10 million or so rRNAs per cell.