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Proc Natl Acad Sci U S A. 2019 Apr 16;116(16):7889-7898. doi: 10.1073/pnas.1821038116. Epub 2019 Mar 29.

Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties.

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Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305;
Department of Biomedical Engineering, Washington University, St. Louis, MO 63130.
Center for Science & Engineering of Living Systems, Washington University, St. Louis, MO 63130.
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.
Department of Anatomy, University of California, San Francisco, CA 94143.
Center for Structural Biology, Vlaams Instituut voor Biotechnologie, Vrije Universiteit Brussel, B-1050 Brussels, Belgium.
Laboratory of Neurobiology, Center for Brain & Disease Research, Vlaams Instituut voor Biotechnologie, 3000 Leuven, Belgium.
Experimental Neurology, Department of Neurosciences, KU Leuven, 3001 Leuven, Belgium.
Department of Biochemistry, Stanford University, Stanford, CA 94305.
Department of Physics, Stanford University, Stanford, CA 94305.
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary.
Department of Biomedical Engineering, Washington University, St. Louis, MO 63130;


Phase separation of multivalent protein and RNA molecules underlies the biogenesis of biomolecular condensates such as membraneless organelles. In vivo, these condensates encompass hundreds of distinct types of molecules that typically organize into multilayered structures supporting the differential partitioning of molecules into distinct regions with distinct material properties. The interplay between driven (active) versus spontaneous (passive) processes that are required for enabling the formation of condensates with coexisting layers of distinct material properties remains unclear. Here, we deploy systematic experiments and simulations based on coarse-grained models to show that the collective interactions among the simplest, biologically relevant proteins and archetypal RNA molecules are sufficient for driving the spontaneous emergence of multilayered condensates with distinct material properties. These studies yield a set of rules regarding homotypic and heterotypic interactions that are likely to be relevant for understanding the interplay between active and passive processes that control the formation of functional biomolecular condensates.


RNA; biomolecular condensates; complex coacervation; intrinsically disordered proteins; phase transitions

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