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

Nat Struct Mol Biol. 2019 Mar;26(3):220-226. doi: 10.1038/s41594-019-0193-2. Epub 2019 Mar 4.

Abstract

RNA granules are subcellular compartments that are proposed to form by liquid-liquid phase separation (LLPS), a thermodynamic process that partitions molecules between dilute liquid phases 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 Caenorhabditis elegans embryos. Theoretical studies have suggested that spontaneous LLPS of the RNA-binding protein PGL-3 with RNA drives the assembly of P granules. 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 phases and liquid phases confers local stability and long-range dynamics, both of which contribute to localized assembly of P granules. Our findings suggest that condensation of RNA granules can be regulated spatially by gel-like polymers that stimulate LLPS locally in the cytoplasm.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Cytoplasm / metabolism
  • Liquid-Liquid Extraction
  • RNA / metabolism*
  • RNA-Binding Proteins / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • MEG-3 protein, C elegans
  • PGL-3 protein, C elegans
  • RNA-Binding Proteins
  • RNA