Abstract
Biomolecular condensation partitions cellular contents and has important roles in stress responses, maintaining homeostasis, development and disease. Many nuclear and cytoplasmic condensates are rich in RNA and RNA-binding proteins (RBPs), which undergo liquid–liquid phase separation (LLPS). Whereas the role of RBPs in condensates has been well studied, less attention has been paid to the contribution of RNA to LLPS. In this Review, we discuss the role of RNA in biomolecular condensation and highlight considerations for designing condensate reconstitution experiments. We focus on RNA properties such as composition, length, structure, modifications and expression level. These properties can modulate the biophysical features of native condensates, including their size, shape, viscosity, liquidity, surface tension and composition. We also discuss the role of RNA–protein condensates in development, disease and homeostasis, emphasizing how their properties and function can be determined by RNA. Finally, we discuss the multifaceted cellular functions of biomolecular condensates, including cell compartmentalization through RNA transport and localization, supporting catalytic processes, storage and inheritance of specific molecules, and buffering noise and responding to stress.
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Acknowledgements
The authors thank C. Iserman for critical reading of this manuscript. This work has been funded by the NIH National Institute of General Medical Sciences (R01-GM081506, A.S.G.; F32 F32GM136164, C.R.), Howard Hughes Medical Institute Faculty Scholars program (A.S.G.), University of North Carolina at Chapel Hill (T32 CA 9156-43, C.R.) and the L’Oreal Women in Science Fellowship (C.R). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
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Glossary
- Intrinsically disordered regions
-
(IDRs). Sequences of RNA or protein that lack defined 3D order or structure.
- P granules
-
Non-membrane-bound presumptive germ cell granules.
- Re-entrant phase behaviour
-
The behaviour seen when sufficiently high concentrations of a component, such as RNA, prevent condensation, in many cases owing to charge repulsion effects.
- Phase diagrams
-
Charts used to show the state of a mixture at equilibrium, depending on particular conditions; for biomolecular condensates, this state is often a function of the concentration of mixture components such as protein and RNA.
- Stress granules
-
Membraneless condensates consisting of RNA and protein that appear in cells in conditions of stress.
- Paraspeckles
-
Membraneless condensates consisting of RNA and protein in interphase nuclei; scaffolded by the long non-coding RNA NEAT1.
- Microspeckles
-
Membraneless condensates consisting of RNA and protein in interphase nuclei; scaffolded by the long non-coding RNA NEAT1 splicing isoform 1-1.
- G-quadruplex
-
A nucleic acid, four-stranded structure formed by guanine-rich sequences.
- Condensed phase
-
A solid or liquid condensate that forms by electrostatic interactions and demixing from solution.
- Dilute phase
-
The molecules remaining in solution, unincorporated into either solid or liquid condensates.
- Speckles
-
Membraneless condensates in the nucleus that store and modify splicing factors.
- Cajal bodies
-
(Also known as coiled bodies). Membraneless nuclear bodies containing RNA and protein that are sites of post-transcriptional modification of small nuclear and nucleolar RNAs.
- PML bodies
-
Membraneless bodies consisting of RNA and protein and scaffolded by the promyelocytic leukaemia (PML) protein. May have roles in apoptosis, cell division and response to viral infection.
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Roden, C., Gladfelter, A.S. RNA contributions to the form and function of biomolecular condensates. Nat Rev Mol Cell Biol 22, 183–195 (2021). https://doi.org/10.1038/s41580-020-0264-6
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DOI: https://doi.org/10.1038/s41580-020-0264-6
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