RNA length has a non-trivial effect in the stability of biomolecular condensates formed by RNA-binding proteins.
Publication Date
2022-02Journal Title
PLoS Comput Biol
ISSN
1553-734X
Publisher
Public Library of Science (PLoS)
Volume
18
Issue
2
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Sanchez-Burgos, I., Espinosa, J. R., Joseph, J. A., & Collepardo-Guevara, R. (2022). RNA length has a non-trivial effect in the stability of biomolecular condensates formed by RNA-binding proteins.. PLoS Comput Biol, 18 (2) https://doi.org/10.1371/journal.pcbi.1009810
Description
Funder: Oppenheimer Fellowship
Funder: Roger Ekins Fellowship
Funder: Derek Brewer Emmanuel College scholarship
Abstract
Biomolecular condensates formed via liquid-liquid phase separation (LLPS) play a crucial role in the spatiotemporal organization of the cell material. Nucleic acids can act as critical modulators in the stability of these protein condensates. To unveil the role of RNA length in regulating the stability of RNA binding protein (RBP) condensates, we present a multiscale computational strategy that exploits the advantages of a sequence-dependent coarse-grained representation of proteins and a minimal coarse-grained model wherein proteins are described as patchy colloids. We find that for a constant nucleotide/protein ratio, the protein fused in sarcoma (FUS), which can phase separate on its own-i.e., via homotypic interactions-only exhibits a mild dependency on the RNA strand length. In contrast, the 25-repeat proline-arginine peptide (PR25), which does not undergo LLPS on its own at physiological conditions but instead exhibits complex coacervation with RNA-i.e., via heterotypic interactions-shows a strong dependence on the length of the RNA strands. Our minimal patchy particle simulations suggest that the strikingly different effect of RNA length on homotypic LLPS versus RBP-RNA complex coacervation is general. Phase separation is RNA-length dependent whenever the relative contribution of heterotypic interactions sustaining LLPS is comparable or higher than those stemming from protein homotypic interactions. Taken together, our results contribute to illuminate the intricate physicochemical mechanisms that influence the stability of RBP condensates through RNA inclusion.
Keywords
Research Article, Biology and life sciences, Computer and information sciences, Physical sciences
Sponsorship
Engineering and Physical Sciences Research Council (EP/P020259/1)
European Research Council (803326)
EPSRC (EP/T517847/1)
Identifiers
pcompbiol-d-21-01836
External DOI: https://doi.org/10.1371/journal.pcbi.1009810
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334677
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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