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dc.contributor.authorTejedor, Andrés R
dc.contributor.authorGaraizar, Adiran
dc.contributor.authorRamírez, Jorge
dc.contributor.authorEspinosa, Jorge R
dc.date.accessioned2021-11-09T00:30:29Z
dc.date.available2021-11-09T00:30:29Z
dc.date.issued2021-12-07
dc.identifier.issn0006-3495
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330465
dc.description.abstractOne 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.
dc.description.sponsorshipEPSRC
dc.publisherElsevier BV
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.title'RNA modulation of transport properties and stability in phase-separated condensates.
dc.typeArticle
prism.publicationNameBiophys J
dc.identifier.doi10.17863/CAM.77909
dcterms.dateAccepted2021-10-03
rioxxterms.versionofrecord10.1016/j.bpj.2021.11.003
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-11-02
dc.contributor.orcidRene Espinosa, Jorge [0000-0001-9530-2658]
dc.identifier.eissn1542-0086
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/N509620/1)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/P020259/1)
cam.orpheus.successTue Feb 01 19:02:12 GMT 2022 - Embargo updated*
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rioxxterms.freetoread.startdate2022-12-07


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