Compositional Control of Phase-Separated Cellular Bodies

Cell. 2016 Jul 28;166(3):651-663. doi: 10.1016/j.cell.2016.06.010. Epub 2016 Jun 30.


Cellular bodies such as P bodies and PML nuclear bodies (PML NBs) appear to be phase-separated liquids organized by multivalent interactions among proteins and RNA molecules. Although many components of various cellular bodies are known, general principles that define body composition are lacking. We modeled cellular bodies using several engineered multivalent proteins and RNA. In vitro and in cells, these scaffold molecules form phase-separated liquids that concentrate low valency client proteins. Clients partition differently depending on the ratio of scaffolds, with a sharp switch across the phase diagram diagonal. Composition can switch rapidly through changes in scaffold concentration or valency. Natural PML NBs and P bodies show analogous partitioning behavior, suggesting how their compositions could be controlled by levels of PML SUMOylation or cellular mRNA concentration, respectively. The data suggest a conceptual framework for considering the composition and control thereof of cellular bodies assembled through heterotypic multivalent interactions.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Artificial Cells / chemistry*
  • Body Composition
  • Carrier Proteins / chemistry
  • Cell Compartmentation*
  • Cell Line
  • Cell Nucleus / chemistry
  • Cytoplasm
  • Electrochemistry
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Molecular Structure
  • Organelles / chemistry*
  • Polypyrimidine Tract-Binding Protein / chemistry
  • Protein Engineering
  • Proteins / chemistry*
  • Ubiquitins / chemistry
  • Yeasts


  • Carrier Proteins
  • Proteins
  • SIMC1 protein, human
  • SUMO3 protein, human
  • Ubiquitins
  • Polypyrimidine Tract-Binding Protein