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‘RNA modulation of transport properties and stability in phase-separated condensates

One of the key mechanisms employed by cells to control their spatiotemporal organization is the formation and dissolution of phase-separated condensates. The balance between condensate assembly and disassembly can be critically regulated by the presence of RNA. In this work, we use a chemically-accu...

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Autores principales: Tejedor, Andrés R., Garaizar, Adiran, Ramírez, Jorge, Espinosa, Jorge R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715277/
https://www.ncbi.nlm.nih.gov/pubmed/34762868
http://dx.doi.org/10.1016/j.bpj.2021.11.003
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author Tejedor, Andrés R.
Garaizar, Adiran
Ramírez, Jorge
Espinosa, Jorge R.
author_facet Tejedor, Andrés R.
Garaizar, Adiran
Ramírez, Jorge
Espinosa, Jorge R.
author_sort Tejedor, Andrés R.
collection PubMed
description One of the key mechanisms employed by cells to control their spatiotemporal organization is the formation and dissolution of phase-separated condensates. The balance between condensate assembly and disassembly can be critically regulated by the presence of RNA. In this work, we use a chemically-accurate sequence-dependent coarse-grained model for proteins and RNA to unravel the impact of RNA in modulating the transport properties and stability of biomolecular condensates. We explore the phase behavior of several RNA-binding proteins such as FUS, hnRNPA1, and TDP-43 proteins along with that of their corresponding prion-like domains and RNA recognition motifs from absence to moderately high RNA concentration. By characterizing the phase diagram, key molecular interactions, surface tension, and transport properties of the condensates, we report a dual RNA-induced behavior: on the one hand, RNA enhances phase separation at low concentration as long as the RNA radius of gyration is comparable to that of the proteins, whereas at high concentration, it inhibits the ability of proteins to self-assemble independently of its length. On the other hand, along with the stability modulation, the viscosity of the condensates can be considerably reduced at high RNA concentration as long as the length of the RNA chains is shorter than that of the proteins. Conversely, long RNA strands increase viscosity even at high concentration, but barely modify protein self-diffusion which mainly depends on RNA concentration and on the effect RNA has on droplet density. On the whole, our work rationalizes the different routes by which RNA can regulate phase separation and condensate dynamics, as well as the subsequent aberrant rigidification implicated in the emergence of various neuropathologies and age-related diseases.
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spelling pubmed-87152772022-12-07 ‘RNA modulation of transport properties and stability in phase-separated condensates Tejedor, Andrés R. Garaizar, Adiran Ramírez, Jorge Espinosa, Jorge R. Biophys J Articles One of the key mechanisms employed by cells to control their spatiotemporal organization is the formation and dissolution of phase-separated condensates. The balance between condensate assembly and disassembly can be critically regulated by the presence of RNA. In this work, we use a chemically-accurate sequence-dependent coarse-grained model for proteins and RNA to unravel the impact of RNA in modulating the transport properties and stability of biomolecular condensates. We explore the phase behavior of several RNA-binding proteins such as FUS, hnRNPA1, and TDP-43 proteins along with that of their corresponding prion-like domains and RNA recognition motifs from absence to moderately high RNA concentration. By characterizing the phase diagram, key molecular interactions, surface tension, and transport properties of the condensates, we report a dual RNA-induced behavior: on the one hand, RNA enhances phase separation at low concentration as long as the RNA radius of gyration is comparable to that of the proteins, whereas at high concentration, it inhibits the ability of proteins to self-assemble independently of its length. On the other hand, along with the stability modulation, the viscosity of the condensates can be considerably reduced at high RNA concentration as long as the length of the RNA chains is shorter than that of the proteins. Conversely, long RNA strands increase viscosity even at high concentration, but barely modify protein self-diffusion which mainly depends on RNA concentration and on the effect RNA has on droplet density. On the whole, our work rationalizes the different routes by which RNA can regulate phase separation and condensate dynamics, as well as the subsequent aberrant rigidification implicated in the emergence of various neuropathologies and age-related diseases. The Biophysical Society 2021-12-07 2021-11-09 /pmc/articles/PMC8715277/ /pubmed/34762868 http://dx.doi.org/10.1016/j.bpj.2021.11.003 Text en © 2021. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles
Tejedor, Andrés R.
Garaizar, Adiran
Ramírez, Jorge
Espinosa, Jorge R.
‘RNA modulation of transport properties and stability in phase-separated condensates
title ‘RNA modulation of transport properties and stability in phase-separated condensates
title_full ‘RNA modulation of transport properties and stability in phase-separated condensates
title_fullStr ‘RNA modulation of transport properties and stability in phase-separated condensates
title_full_unstemmed ‘RNA modulation of transport properties and stability in phase-separated condensates
title_short ‘RNA modulation of transport properties and stability in phase-separated condensates
title_sort ‘rna modulation of transport properties and stability in phase-separated condensates
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715277/
https://www.ncbi.nlm.nih.gov/pubmed/34762868
http://dx.doi.org/10.1016/j.bpj.2021.11.003
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