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The fitness cost and benefit of phase-separated protein deposits

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dc.contributor.author Sanchez de Groot, Natalia
dc.contributor.author Torrent, Marc
dc.contributor.author Ravarani, Charles N.J.
dc.contributor.author Trusina, Ala
dc.contributor.author Ventura, Salvador
dc.contributor.author Babu, M. Madan
dc.date.accessioned 2019-07-19T08:33:40Z
dc.date.available 2019-07-19T08:33:40Z
dc.date.issued 2019
dc.identifier.citation Sanchez de Groot N, Torrent Burgas M, Ravarani CN, Trusina A, Ventura S, Babu MM. The fitness cost and benefit of phase-separated protein deposits. Mol Syst Biol. 2019 Apr 8;15(4):e8075. DOI: 10.15252/msb.20178075
dc.identifier.issn 1744-4292
dc.identifier.uri http://hdl.handle.net/10230/42069
dc.description.abstract Phase separation of soluble proteins into insoluble deposits is associated with numerous diseases. However, protein deposits can also function as membrane-less compartments for many cellular processes. What are the fitness costs and benefits of forming such deposits in different conditions? Using a model protein that phase-separates into deposits, we distinguish and quantify the fitness contribution due to the loss or gain of protein function and deposit formation in yeast. The environmental condition and the cellular demand for the protein function emerge as key determinants of fitness. Protein deposit formation can influence cell-to-cell variation in free protein abundance between individuals of a cell population (i.e., gene expression noise). This results in variable manifestation of protein function and a continuous range of phenotypes in a cell population, favoring survival of some individuals in certain environments. Thus, protein deposit formation by phase separation might be a mechanism to sense protein concentration in cells and to generate phenotypic variability. The selectable phenotypic variability, previously described for prions, could be a general property of proteins that can form phase-separated assemblies and may influence cell fitness.
dc.description.sponsorship This work was supported by the Medical Research Council (MC_U105185859; M.M.B., M.T., C.R., and N.S.G.), Marie Curie Actions (FP7-PEOPLE-2012- IEF-330352, to M.T.; and FP7-PEOPLE-2011-IEF299105, to N.S.G.), FEBS LongTerm Fellowships (N.S.G.), Beatriu de Pinos fellowships (M.T.), and the Ministerio de Economía y Competitividad (SAF2017-82158-R, SAF2015-72518-EXP, and RYC-2012-09999; M.T.). N.S.G. is a recipient of the MRC Centenary Award. M.M.B. is a Lister Institute Research Prize Fellow. We thank Gian Gaetano for supporting N.S.G. and Sean Munro for the gift of strain Y03157
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Wiley-VCH Verlag
dc.relation.ispartof Molecular Systems Biology. 2019 Apr 8;15(4):e8075
dc.rights © 2019 MRC Laboratory of Molecular Biology. Published under the terms of the CC BY 4.0 license
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Fitnes
dc.subject.other Selecció natural
dc.subject.other Fenotip
dc.subject.other Proteïnes
dc.subject.other Genètica
dc.title The fitness cost and benefit of phase-separated protein deposits
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.15252/msb.20178075
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-82158-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-72518-EXP
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/RYC-2012-09999
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/330352
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/299105
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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