Compositional Control of Phase-Separated Cellular Bodies

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. W...

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Bibliographic Details
Published in:Cell 2016-07, Vol.166 (3), p.651-663
Main Authors: Banani, Salman F., Rice, Allyson M., Peeples, William B., Lin, Yuan, Jain, Saumya, Parker, Roy, Rosen, Michael K.
Format: Article
Language:English
Subjects:
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
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Summary: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. [Display omitted] •Cellular bodies are organized by scaffolds and recruit clients•Clients bind to free sites in the scaffolds, and binding scales with client valency•Relative scaffold stoichiometries control client recruitment in switch-like fashion•Cells can control these parameters and thus regulate cellular body composition What are the general principles that define the composition of phase-separated cellular bodies?
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2016.06.010