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Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1

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Gulyurtlu_2022_DMM_Stressgranules_CC.pdf (13.76Mb)
Date
02/08/2022
Author
Gulyurtlu, Selma
Magon, Monika S.
Guest, Patrick Neville
Papavasiliou, Panagiotis P.
Morrison, Kim
Prescott, Alan
Sleeman, Judith E.
Funder
Muscular Dystrophy UK
The Wellcome Trust
Grant ID
16RGO-PG36-65
105621/Z/14/Z
Keywords
LLPS
Myotonic Dystrophy Type-1
P-bodies
Stress granules
Trinucleotide repeats
QH301 Biology
NDAS
Metadata
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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 DM1 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 (SGs) 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 SGs suggest an altered ability of cells to respond to stress associated with DM1, while changes to the structure and dynamics of SGs and P-bodies suggest that a widespread alteration to the biophysical properties of cellular structures may be a consequence of the presence of CUGexp RNA.
Citation
Gulyurtlu , S , Magon , M S , Guest , P N , Papavasiliou , P P , Morrison , K , Prescott , A & Sleeman , J E 2022 , ' Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1 ' , Disease Models & Mechanisms , vol. 15 , no. 7 , dmm049294 . https://doi.org/10.1242/dmm.049294
Publication
Disease Models & Mechanisms
Status
Peer reviewed
DOI
https://doi.org/10.1242/dmm.049294
ISSN
1754-8403
Type
Journal article
Rights
Copyright © 2022 The Author(s). Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Description
This work was supported by Muscular Dystrophy UK (project grant number 16GRO-PG360065 to JES), BBSRC (EASTBIO DTP studentship award to SG) and the Wellcome Trust (ISSF award 105621/Z/14/Z to JES and PG).
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/25830

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