Gene

Globular protein

Cajal body

Physics

Biophysics

Philosophy

Valency

Function (biology)

Computational chemistry

Chemical physics

Organic chemistry

Chemistry

Biological system

Condensation

Complementarity (molecular biology)

Macromolecule

Linguistics

Phase (matter)

Genetics

RNA splicing

Biochemistry

Molecular dynamics

Crystallography

Biology

Cell biology

Thermodynamics

eLife

Phase separation processes are increasingly being recognized as important organizing mechanisms of biological macromolecules in cellular environments. Well-established drivers of phase separation are multi-valency and intrinsic disorder. Here, we show that globular macromolecules may condense simply based on electrostatic complementarity. More specifically, phase separation of mixtures between RNA and positively charged proteins is described from a combination of multiscale computer simulations with microscopy and spectroscopy experiments. Phase diagrams were mapped out as a function of molecular concentrations in experiment and as a function of molecular size and temperature via simulations. The resulting condensates were found to retain at least some degree of internal dynamics varying as a function of the molecular composition. The results suggest a more general principle for phase separation that is based primarily on electrostatic complementarity without invoking polymer properties as in most previous studies. Simulation results furthermore suggest that such phase separation may occur widely in heterogenous cellular environment between nucleic acid and protein components.

Charge-driven condensation of RNA and proteins suggests broad role of phase separation in cytoplasmic environments