The "structural" journey of a ribonucleoprotein complex: From molecules to droplets.

Abstract

Our current models for the formation of ribonucleoprotein (RNP) granules by liquid-liquid phase separation do not include the early assembly steps that often involve a nucleation-and-growth mechanism. This is due to the challenges in characterizing the structure and dynamics of RNA-protein complexes that kick-start condensate assembly. To tackle this challenge, we chose a model system comprising a highly conserved IDR-containing protein, SERF, and structured and single-stranded RNA elements. We find that multiple SERF molecules bind RNA by electrostatic forces to form a compact and dynamic complex. This RNA-protein complex acts as a nucleus to seed macroscopic condensates by complex coacervation. Interestingly, we have previously shown that SERF accelerates primary nucleation of amyloid proteins, a property that had led to SERF's discovery as a modifier of amyloid toxicity in C. elegans. Future work will explore the parallels between SERF's interaction with RNA and amyloid proteins and uncover the mechanistic role of disorder in the phase transitions of SERF.