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bioRxiv · 10.1101/2021.06.14.448303

Phase-separated stress granules and processing bodies are compromised in Myotonic Dystrophy Type 1

Gulyurtlu, S.·Magon, M. S.·Guest, P.·Papavasiliou, P. P.·Prescott, A. R.·Sleeman, J. E.
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Abstract

RNA regulation in mammalian cells requires complex physical compartmentalisation using structures thought to be formed by liquid-liquid phase separation. Disruption of these structures is implicated in numerous degenerative diseases. Myotonic Dystrophy Type 1 (DM1) is a multi-systemic trinucleotide repeat disorder resulting from a CTG expansion in the dystonia myotonica protein kinase gene (DMPK). The cellular hall-mark of DM1 is the formation of nuclear foci containing expanded DMPK RNA (CUGexp). We report here the deregulation of stress granules and processing bodies (P-bodies), two cytoplasmic structures key for mRNA regulation, in cell culture models of DM1. Alterations to the rates of formation and dispersal of stress granules suggest an altered ability to respond to stress associated with DM1, while changes to the structure and dynamics of stress granules and P-bodies suggest that a more widespread alteration to the biophysical properties of cellular structures may be a consequence of the presence of CUGexp RNA.

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Gulyurtlu, S., Magon, M. S., Guest, P., Papavasiliou, P. P., Prescott, A. R., Sleeman, J. E.. 2021-06-15. Phase-separated stress granules and processing bodies are compromised in Myotonic Dystrophy Type 1. https://doi.org/10.1101/2021.06.14.448303

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