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Biochemical Timekeeping Via Reentrant Phase Transitions
Affiliation:1. Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;2. Technische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Biotechnology Center, 01307 Dresden, Germany;3. University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;4. Marine Biological Laboratory, Woods Hole, MA 02543, USA;5. Department for Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA;1. Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA;2. Department of Physics, Washington University in St. Louis, St. Louis, MO 63130, USA;3. Department of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA;4. Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN 38103, USA;1. Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland;2. Biocentre, Johannes Gutenberg University Mainz, Mainz, Germany;3. Institute of Molecular Biology, Mainz, Germany;4. Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri;5. Center for Science & Engineering of Living Systems, Washington University in St. Louis, St. Louis, Missouri;1. Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;2. Department of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA;3. Research Institute of Molecular Pathology, Campus-Vienna-Biocenter 1, 1030 Vienna, Austria;1. The HHMI Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA;2. Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;3. Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA;4. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA;1. Department of Biomedical Engineering and Center for Science & Engineering of Living Systems, Washington University in St. Louis, St. Louis, MO 63130, USA;2. Department of Physics, Washington University in St. Louis, St. Louis, MO 63130, USA;3. Stowers Institute for Medical Research, Kansas City, MO 64110, USA;4. The Open University, Milton Keynes MK7 6AA, United Kingdom;5. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA
Abstract:Appreciation for the role of liquid–liquid phase separation in the functional organization of cellular matter has exploded in recent years. More recently there has been a growing effort to understand the principles of heterotypic phase separation, the demixing of multiple proteins and nucleic acids into a single functional condensate. A phase transition is termed reentrant if it involves the transformation of a system from one state into a macroscopically similar or identical state via at least two phase transitions elicited by variation of a single parameter. Reentrant liquid–liquid phase separation can occur when the condensation of one species is tuned by another. Reentrant phase transitions have been modeled in vitro using protein and RNA mixtures. These biochemical studies reveal two features of reentrant phase separation that are likely important to functional cellular condensates: (1) the ability to generate condensates with layered functional topologies, and (2) the ability to generate condensates whose composition and duration are self-limiting to enable a form of biochemical timekeeping. We relate these biochemical studies to potential cellular examples and discuss how layered topologies and self-regulation may impact key biological processes.
Keywords:phase separation  reentrant phase transitions  disordered proteins  transcription  RNA  condensates
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