A gel phase promotes condensation of liquid P granules in C. elegans embryos

RNA granules are sub-cellular compartments proposed to form by liquid-liquid phase separation (LLPS), a thermodynamic process that partitions molecules between dilute and condensed liquid phases. The mechanisms that localize liquid phases in cells, however, are not fully understood. P granules are RNA granules that form in the posterior of C. elegans embryos. Theoretical studies have suggested that spontaneous LLPS of the RNA-binding protein PGL-3 with RNA drives P granule assembly. We find that the PGL-3 phase is intrinsically labile and requires a second phase for stabilization in embryos. The second phase is formed by gel-like assemblies of the disordered protein MEG-3 that associate with liquid PGL-3 droplets in the embryo posterior. Co-assembly of gel and liquid phases confers local stability and long-range dynamics, both of which contribute to localized P granule assembly. Our findings suggest that condensation of RNA granules can be regulated spatially by gel-like polymers that stimulate LLPS locally in the cytoplasm.