University of Cambridge > Talks.cam > Biophysical Seminars > Dr Jekyll and Mr Hyde: RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43

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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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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