ABSTRACT
Phase separation of globular RNA and positively charged proteins is reported from a combination of coarse-grained simulations parametrized based on atomistic simulations, theory informed by the coarse-grained simulations, and experimental validation via confocal microscopy and FRET spectroscopy. Phase separation is found to depend on concentration, size, and charge of the proteins, requiring a minimum protein size, minimum protein charge, and minimum protein concentration before condensates can form. The general principle for phase separation is based on electrostatic complementarity rather than invoking polymer character as in most previous studies. Simulation results furthermore suggest that such phase separation may occur in heterogenous cellular environment, not just between tRNA and cellular proteins but also between ribosomes and proteins where there may be competition for positively charged proteins.
STATEMENT OF SIGNIFICANCE Liquid-liquid phase separation has been recognized as a key mechanism for forming membrane-less organelles in cells. Commonly discussed mechanisms invoke a role of disordered peptides and specific multi-valent interactions. We report here phase separation of RNA and proteins based on a more universal principle of charge complementarity that does not require disorder or specific interactions. The findings are supported by coarse-grained simulations, theory, and experimental validation via microscopy and FRET spectroscopy. The implications of this work are that condensate formation may be an even more universal phenomenon in biological systems than thought to date.
Competing Interest Statement
The authors have declared no competing interest.
