Title:
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RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43
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Author:
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Zacco, Elsa; Graña-Montes, Ricardo; Martin, Stephen R.; Sanchez de Groot, Natalia; Alfano, Caterina; Tartaglia, Gian Gaetano; Pastore, Annalisa
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Abstract:
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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. |
Abstract:
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This work was supported by a Newton International Fellowship (Royal Society) and the European Research Council (ERC, Ribomylome) |
Subject(s):
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-Esclerosi lateral amiotròfica -Demència frontotemporal -Sistema nerviós -- Degeneració -Agregació de proteïnes -RNA |
Rights:
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© 2019 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Document type:
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Article Article - Accepted version |
Published by:
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Elsevier
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