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

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...

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Autores principales: Gulyurtlu, Selma, Magon, Monika S., Guest, Patrick, Papavasiliou, Panagiotis P., Morrison, Kim D., Prescott, Alan R., Sleeman, Judith E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366894/
https://www.ncbi.nlm.nih.gov/pubmed/35642886
http://dx.doi.org/10.1242/dmm.049294
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author Gulyurtlu, Selma
Magon, Monika S.
Guest, Patrick
Papavasiliou, Panagiotis P.
Morrison, Kim D.
Prescott, Alan R.
Sleeman, Judith E.
author_facet Gulyurtlu, Selma
Magon, Monika S.
Guest, Patrick
Papavasiliou, Panagiotis P.
Morrison, Kim D.
Prescott, Alan R.
Sleeman, Judith E.
author_sort Gulyurtlu, Selma
collection PubMed
description 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 an expansion of nucleotides CTG (CTGexp) in the DNA encoding DM1 protein kinase (DMPK). The cellular hallmark of DM1 is the formation of nuclear foci that contain expanded DMPK RNA (CUGexp) (with thymine instead of uracil). 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 is a consequence of the presence of CUGexp RNA.
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spelling pubmed-93668942022-08-11 Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1 Gulyurtlu, Selma Magon, Monika S. Guest, Patrick Papavasiliou, Panagiotis P. Morrison, Kim D. Prescott, Alan R. Sleeman, Judith E. Dis Model Mech Research Article 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 an expansion of nucleotides CTG (CTGexp) in the DNA encoding DM1 protein kinase (DMPK). The cellular hallmark of DM1 is the formation of nuclear foci that contain expanded DMPK RNA (CUGexp) (with thymine instead of uracil). 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 is a consequence of the presence of CUGexp RNA. The Company of Biologists Ltd 2022-08-02 /pmc/articles/PMC9366894/ /pubmed/35642886 http://dx.doi.org/10.1242/dmm.049294 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Research Article
Gulyurtlu, Selma
Magon, Monika S.
Guest, Patrick
Papavasiliou, Panagiotis P.
Morrison, Kim D.
Prescott, Alan R.
Sleeman, Judith E.
Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1
title Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1
title_full Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1
title_fullStr Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1
title_full_unstemmed Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1
title_short Condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1
title_sort condensation properties of stress granules and processing bodies are compromised in myotonic dystrophy type 1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366894/
https://www.ncbi.nlm.nih.gov/pubmed/35642886
http://dx.doi.org/10.1242/dmm.049294
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