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A framework for understanding the functions of biomolecular condensates across scales
Open accessAbstract
Biomolecular condensates are found throughout eukaryotic cells, including in the nucleus, in the cytoplasm and on membranes. They are also implicated in a wide range of cellular functions, organizing molecules that act in processes ranging from RNA metabolism to signalling to gene regulation. Early work in the field focused on identifying condensates and understanding how their physical properties and regulation arise from molecular constituents. Recent years have brought a focus on understanding condensate functions. Studies have revealed functions that span different length scales: from molecular (modulating the rates of chemical reactions) to mesoscale (organizing large structures within cells) to cellular (facilitating localization of cellular materials and homeostatic responses). In this Roadmap, we discuss representative examples of biochemical and cellular functions of biomolecular condensates from the recent literature and organize these functions into a series of non-exclusive classes across the different length scales. We conclude with a discussion of areas of current interest and challenges in the field, and thoughts about how progress may be made to further our understanding of the widespread roles of condensates in cell biology.
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“The second systems biology criterion follows from the observation that integrated function is only possible via structured spatial heterogeneity, that is, that spatial heterogeneity is crucial to cellular function.”
From ‘Whole Organism’, Systems Biology, and Top-Down Criteria for Evaluating Scenarios for the Origin of Life (2021) · cites this paper as [45]
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Machine learning solutions for predicting protein–protein interactions
Casadio, R., Martelli, P. L., & Savojardo, C. (2022) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1618 · Cited by 83
“The second definition is based on the computation of inter-residue distances: interface residues are those having at least one residue of another subunit at a distance below a defined threshold (routinely between 5 and 8 Å).”
BackgroundInfluentialATP-responsive biomolecular condensates tune bacterial kinase signaling
Saurabh, S., Chong, T. N., Bayas, C. A., Dahlberg, P. D., Cartwright, H. N., Moerner, W. E., & Shapiro, L. (2022) · Science Advances · doi:10.1126/sciadv.abm6570 · Cited by 79
“The observation of glucosedependent regulation of DivJ activity suggested that SpmX exhibited an environmental response, which is often observed in condensates containing IDRs (2).”
BackgroundMethodInfluentialField, S., Jang, G., Dean, C., Strader, L. C., & Rhee, S. Y. (2023) · The Plant Cell · doi:10.1093/plcell/koad062 · Cited by 80
“First, biomolecular condensates sequester proteins (or ligands, e.g. RNA) away from their target, preventing a reaction or signal from occurring (Banani et al. 2017; Lyon et al. 2020; Roden and Gladfelter 2020).”
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Liquid-Liquid Phase Separation: Unraveling the Enigma of Biomolecular Condensates in Microbial Cells
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Mammalian IRE1α dynamically and functionally coalesces with stress granules
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An Introduction to the Stickers-and-Spacers Framework as Applied to Biomolecular Condensates
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Accessory proteins of the RAS-MAPK pathway: moving from the side line to the front line
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A Unified Description of Salt Effects on the Liquid–Liquid Phase Separation of Proteins
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“through which plenty of biomolecular condensates can be assembled [1, 2].”
BackgroundQuantitative theory for the diffusive dynamics of liquid condensates
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Phase Transitions in Chemically Fueled, Multiphase Complex Coacervate Droplets
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“34,35,88,89 90 – 92 Traf fi c into and out of the nucleus occurs through nuclear pore complexes that span the two membrane bilayers of the nuclear envelope.”
Membrane-associated phase separation: organization and function emerge from a two-dimensional milieu
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Phospholipid Membrane Formation Templated by Coacervate Droplets
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Liquid–liquid phase separation in plants: Advances and perspectives from model species to crops
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“Multivalent interactions play a central role in driving biomolecules to undergo LLPS (Lyon et al., 2021).”
BackgroundMaterial properties of biomolecular condensates emerge from nanoscale dynamics
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Cytoplasmic forces functionally reorganize nuclear condensates in oocytes
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“These forces enhance the mobility of the nucleolus 11 , one of many nuclear liquid-like compartments of RNA processing knownas biomolecular condensates 13 – 15 .”
BackgroundDroplet Physics and Intracellular Phase Separation
Jülicher, F., & Weber, C. A. (2023) · Annual Review of Condensed Matter Physics · doi:10.1146/annurev-conmatphys-031720-032917 · Cited by 65
Temperature-dependent reentrant phase transition of RNA–polycation mixtures
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Martini3-IDP: improved Martini 3 force field for disordered proteins
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Avni, A., Joshi, A., Walimbe, A., Pattanashetty, S. G., & Mukhopadhyay, S. (2022) · Nature Communications · doi:10.1038/s41467-022-32143-0 · Cited by 63
Metadata
- Authors
- Lyon, A. S., Peeples, W. B., & Rosen, M. K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Rosen, Michael K.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2020-11-09
- Volume
- 22
- Issue
- 3
- Pages
- 215-235
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC8574987
- OpenAlex
- W3099323319
- Cited by
- 895
- References
- 233
- Citations by year
- 2026: 149 · 2025: 186 · 2024: 175 · 2023: 172 · 2022: 115 · 2021: 95 · 2020: 2
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (F32GM136058)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- biomolecular condensates, liquid-liquid phase separation, length scales, RNA metabolism, gene expression regulation, cell organization, signal transduction, reaction rate, cellular homeostasis
- MeSH terms
- Animals, Biochemical Phenomena, Cell Physiological Phenomena, Cytoplasm, Eukaryotic Cells, Humans, Organelles, Macromolecular Substances, Multiprotein Complexes, Protein Aggregates
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