Compositional Control of Phase-Separated Cellular Bodies

By Salman F. Banani, Allyson M. Rice, William Peeples, Yuan Lin, Saumya Jain, R. Parker, M. Rosen. Cell, 2016

1,096 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/09e646df44bdb3d870683bd2b632927275819e69

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

Intrinsically disordered regions contribute promiscuous interactions to RNP granule assembly (2017, background): “It is notable that components of all of these assemblies are enriched in IDRs (Banani et al., 2016; Hegde et al., 2010; Hnisz et al., 2017; Iakoucheva et al., 2002; Kai, 2016; Minezaki et al., 2006).”
A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins (2018, positive): “This implies that a cell can trigger phase separation of specific proteins and that only certain clients partition into these condensates, whereas others are kept out (Banani et al., 2016; Feric et al., 2016; Zhang et al., 2015).”
Ki-67: more than a proliferation marker (2018, background): “Because sumoylated proteins are implicated in liquid demixing reactions (Banani et al. 2016), these results raise the possibility that p150 can modulate the phase transition properties of Ki-67.”
Random-phase-approximation theory for sequence-dependent, biologically functional liquid-liquid phase separation of intrinsically disordered proteins (2016, background): “They are a form of cell compartmentalization, creating their peculiar microenvironments [34,35] that play critical roles in cellular integrity, homeostasis, gene regulation and the cell cycle.”
G3BP1 is a tunable switch that triggers phase separation to assemble stress granules (2020, neutral): “A “scaffold/client” model was recently advanced based on observations in simple, reconstituted systems where the assembly of condensates was regulated by the valency, concentration, and molar ratio of a small number of scaffold molecules (Banani et al., 2016).”
Coactivator condensation at super-enhancers links phase separation and gene control (2018, background): “Although the exact client-scaffold relationship (54) between these components remains unknown, it is likely that these protein sequences mediate weak multivalent interactions, thereby facilitating condensation.”
The Centrosome Is a Selective Condensate that Nucleates Microtubules by Concentrating Tubulin. (2017, background): “In synthetic SUMO-SIM condensates, the multivalent scaffold component is far more stable than the weakly bound monovalent client proteins, which rapidly exchange with the bulk solution (Banani et al., 2016).”
Liquid phase condensation in cell physiology and disease (2017, background): “If n > m, then there is a higher concentration of SUMO scaffolds with unbound free sites within droplets, resulting in strong recruitment of SIM client molecules.”