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Molecular Mechanisms in Pentanucleotide Repeat Diseases
The number of neurodegenerative diseases resulting from repeat expansion has increased extraordinarily in recent years. In several of these pathologies, the repeat can be transcribed in RNA from both DNA strands producing, at least, one toxic RNA repeat that causes neurodegeneration by a complex mec...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773600/ https://www.ncbi.nlm.nih.gov/pubmed/35053321 http://dx.doi.org/10.3390/cells11020205 |
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author | Loureiro, Joana R. Castro, Ana F. Figueiredo, Ana S. Silveira, Isabel |
author_facet | Loureiro, Joana R. Castro, Ana F. Figueiredo, Ana S. Silveira, Isabel |
author_sort | Loureiro, Joana R. |
collection | PubMed |
description | The number of neurodegenerative diseases resulting from repeat expansion has increased extraordinarily in recent years. In several of these pathologies, the repeat can be transcribed in RNA from both DNA strands producing, at least, one toxic RNA repeat that causes neurodegeneration by a complex mechanism. Recently, seven diseases have been found caused by a novel intronic pentanucleotide repeat in distinct genes encoding proteins highly expressed in the cerebellum. These disorders are clinically heterogeneous being characterized by impaired motor function, resulting from ataxia or epilepsy. The role that apparently normal proteins from these mutant genes play in these pathologies is not known. However, recent advances in previously known spinocerebellar ataxias originated by abnormal non-coding pentanucleotide repeats point to a gain of a toxic function by the pathogenic repeat-containing RNA that abnormally forms nuclear foci with RNA-binding proteins. In cells, RNA foci have been shown to be formed by phase separation. Moreover, the field of repeat expansions has lately achieved an extraordinary progress with the discovery that RNA repeats, polyglutamine, and polyalanine proteins are crucial for the formation of nuclear membraneless organelles by phase separation, which is perturbed when they are expanded. This review will cover the amazing advances on repeat diseases. |
format | Online Article Text |
id | pubmed-8773600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87736002022-01-21 Molecular Mechanisms in Pentanucleotide Repeat Diseases Loureiro, Joana R. Castro, Ana F. Figueiredo, Ana S. Silveira, Isabel Cells Review The number of neurodegenerative diseases resulting from repeat expansion has increased extraordinarily in recent years. In several of these pathologies, the repeat can be transcribed in RNA from both DNA strands producing, at least, one toxic RNA repeat that causes neurodegeneration by a complex mechanism. Recently, seven diseases have been found caused by a novel intronic pentanucleotide repeat in distinct genes encoding proteins highly expressed in the cerebellum. These disorders are clinically heterogeneous being characterized by impaired motor function, resulting from ataxia or epilepsy. The role that apparently normal proteins from these mutant genes play in these pathologies is not known. However, recent advances in previously known spinocerebellar ataxias originated by abnormal non-coding pentanucleotide repeats point to a gain of a toxic function by the pathogenic repeat-containing RNA that abnormally forms nuclear foci with RNA-binding proteins. In cells, RNA foci have been shown to be formed by phase separation. Moreover, the field of repeat expansions has lately achieved an extraordinary progress with the discovery that RNA repeats, polyglutamine, and polyalanine proteins are crucial for the formation of nuclear membraneless organelles by phase separation, which is perturbed when they are expanded. This review will cover the amazing advances on repeat diseases. MDPI 2022-01-08 /pmc/articles/PMC8773600/ /pubmed/35053321 http://dx.doi.org/10.3390/cells11020205 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Loureiro, Joana R. Castro, Ana F. Figueiredo, Ana S. Silveira, Isabel Molecular Mechanisms in Pentanucleotide Repeat Diseases |
title | Molecular Mechanisms in Pentanucleotide Repeat Diseases |
title_full | Molecular Mechanisms in Pentanucleotide Repeat Diseases |
title_fullStr | Molecular Mechanisms in Pentanucleotide Repeat Diseases |
title_full_unstemmed | Molecular Mechanisms in Pentanucleotide Repeat Diseases |
title_short | Molecular Mechanisms in Pentanucleotide Repeat Diseases |
title_sort | molecular mechanisms in pentanucleotide repeat diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773600/ https://www.ncbi.nlm.nih.gov/pubmed/35053321 http://dx.doi.org/10.3390/cells11020205 |
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