Reentrant Liquid Condensation of Ribonucleoprotein–RNA Complexes

Intracellular Ribonucleoprotein (RNP) granules are membrane-less liquid condensates that dynamically form, dissolve, and mature into a gel-like state in response to a changing cellular environment. RNP condensation is largely governed by attractive inter-chain interactions mediated by low-complexity domains. Using an archetypal disordered RNP, fused in sarcoma (FUS), here we employ atomistic simulations to study how RNA, a primary component of RNP granules, can modulate the phase behavior of RNPs by controlling both droplet assembly and dissolution. Electrostatic interactions are found to be the primary driving force behind condensate formation. Monotonically increasing RNA concentration initially leads to droplet assembly via complex coacervation and subsequently triggers an RNP charge inversion, which promotes disassembly. We construct phase diagrams based on Droplet density and Shannon entropy calculations, wherein three distinct regimes can be identified based on RNA and peptide concentrations. Increasing salt concentration is found to inhibit the formation of liquid condensates and narrow the coexistence region. The internal organization and dynamics of the condensates are investigated as a function of RNA/peptide concentrations, RNA chain length and salt concentration.