Charge-driven condensation of RNA and proteins suggests broad role of phase separation in cytoplasmic environments
Abstract
Phase separation processes are increasingly being recognized as important organizing mechanisms of biological macromolecules in cellular environments. Well established drivers of phase separation are multi-valency and intrinsic disorder. Here, we show that globular macromolecules may condense simply based on electrostatic complementarity. More specifically, phase separation of mixtures between RNA and positively charged proteins is described from a combination of multiscale computer simulations with microscopy and spectroscopy experiments. Phase diagrams were mapped out as a function of molecular concentrations in experiment and as a function of molecular size and temperature via simulations. The resulting condensates were found to retain at least some degree of internal dynamics varying as a function of the molecular composition. The results suggest a more general principle for phase separation that is based primarily on electrostatic complementarity without invoking polymer properties as in most previous studies. Simulation results furthermore suggest that such phase separation may occur widely in heterogenous cellular environment between nucleic acid and protein components.
Data availability
All experimental data generated and analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institutes of Health (R35 GM126948)
- Bercem Dutagaci
- Grzegorz Nawrocki
- Michael Feig
National Science Foundation (MCB 1817307)
- Bercem Dutagaci
- Grzegorz Nawrocki
- Joyce Goodluck
- Lisa J Lapidus
- Michael Feig
National Science Foundation (MCB 2018296)
- Charles G Hoogstraten
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Donald Hamelberg, Georgia State University, United States
Publication history
- Received: October 15, 2020
- Accepted: January 25, 2021
- Accepted Manuscript published: January 26, 2021 (version 1)
- Version of Record published: February 10, 2021 (version 2)
Copyright
© 2021, Dutagaci et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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