RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43

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• dc.contributor.author Zacco, Elsa
• dc.contributor.author Graña-Montes, Ricardo
• dc.contributor.author Martin, Stephen R.
• dc.contributor.author Sanchez de Groot, Natalia
• dc.contributor.author Alfano, Caterina
• dc.contributor.author Tartaglia, Gian Gaetano
• dc.contributor.author Pastore, Annalisa
• dc.date.accessioned 2019-07-19T08:33:36Z
• dc.date.available 2019-07-19T08:33:36Z
• dc.date.issued 2019
• dc.description.abstract Amyotrophic lateral sclerosis and frontotemporal lobar degeneration are incurable motor neuron diseases associated with muscle weakness, paralysis and respiratory failure. Accumulation of TAR DNA-binding protein 43 (TDP-43) as toxic cytoplasmic inclusions is one of the hallmarks of these pathologies. TDP-43 is an RNA-binding protein responsible for regulating RNA transcription, splicing, transport and translation. Aggregated TDP-43 does not retain its physiological function. Here, we exploit the ability of TDP-43 to bind specific RNA sequences to validate our hypothesis that the native partners of a protein can be used to interfere with its ability to self-assemble into aggregates. We propose that binding of TDP-43 to specific RNA can compete with protein aggregation. This study provides a solid proof of concept to the hypothesis that natural interactions can be exploited to increase protein solubility and could be adopted as a more general rational therapeutic strategy.
• dc.description.sponsorship This work was supported by a Newton International Fellowship (Royal Society) and the European Research Council (ERC, Ribomylome)
• dc.format.mimetype application/pdf
• dc.identifier.citation Zacco E, Graña-Montes R, Martin SR, de Groot NS, Alfano C, Tartaglia GG et al. RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43. J Mol Biol. 2019 Apr 5;431(8):1671-88. DOI: 10.1016/j.jmb.2019.01.028
• dc.identifier.doi http://dx.doi.org/10.1016/j.jmb.2019.01.028
• dc.identifier.issn 0022-2836
• dc.identifier.uri http://hdl.handle.net/10230/42068
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Journal of Molecular Biology. 2019 Apr 5;431(8):1671-88
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309545
• dc.rights © 2019 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.other Esclerosi lateral amiotròfica
• dc.subject.other Demència frontotemporal
• dc.subject.other Sistema nerviós -- Degeneració
• dc.subject.other Agregació de proteïnes
• dc.subject.other RNA
• dc.title RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion