Dr Jekyll and Mr Hyde: RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43

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• Prof. Annalisa Pastore
• Wednesday 24 October 2018, 10:30-11:30
• Department of Chemistry, Cambridge, Unilever lecture theatre.

If you have a question about this talk, please contact Gabriella Heller.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTD) 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. We exploited 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. Our 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.

This talk is part of the Biophysical Seminars series.

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• Department of Chemistry, Cambridge, Unilever lecture theatre
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