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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.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.issn | 0022-2836 |
dc.identifier.uri | http://hdl.handle.net/10230/42068 |
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.language.iso | eng |
dc.publisher | Elsevier |
dc.relation.ispartof | Journal of Molecular Biology. 2019 Apr 5;431(8):1671-88 |
dc.rights | © 2019 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license |
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.identifier.doi | http://dx.doi.org/10.1016/j.jmb.2019.01.028 |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/309545 |
dc.rights.accessRights | info:eu-repo/semantics/openAccess |
dc.type.version | info:eu-repo/semantics/acceptedVersion |