Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries

Detalhes bibliográficos
Autor(a) principal: Castro, AF
Data de Publicação: 2020
Outros Autores: Loureiro, JR, Bessa, J, Silveira, I
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/143509
Resumo: Unstable repeat expansions and insertions cause more than 30 neurodegenerative and neuromuscular diseases. Remarkably, bidirectional transcription of repeat expansions has been identified in at least 14 of these diseases. More remarkably, a growing number of studies has been showing that both sense and antisense repeat RNAs are able to dysregulate important cellular pathways, contributing together to the observed clinical phenotype. Notably, antisense repeat RNAs from spinocerebellar ataxia type 7, myotonic dystrophy type 1, Huntington’s disease and frontotemporal dementia/amyotrophic lateral sclerosis associated genes have been implicated in transcriptional regulation of sense gene expression, acting either at a transcriptional or posttranscriptional level. The recent evidence that antisense repeat RNAs could modulate gene expression broadens our understanding of the pathogenic pathways and adds more complexity to the development of therapeutic strategies for these disorders. In this review, we cover the amazing progress made in the understanding of the pathogenic mechanisms associated with repeat expansion neurodegenerative and neuromuscular diseases with a focus on the impact of antisense repeat transcription in the development of efficient therapies.
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spelling Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteriesNuclear inclusionsRNA fociSplicing misregulationTrinucleotide repeatsUnstable repeat expansions and insertions cause more than 30 neurodegenerative and neuromuscular diseases. Remarkably, bidirectional transcription of repeat expansions has been identified in at least 14 of these diseases. More remarkably, a growing number of studies has been showing that both sense and antisense repeat RNAs are able to dysregulate important cellular pathways, contributing together to the observed clinical phenotype. Notably, antisense repeat RNAs from spinocerebellar ataxia type 7, myotonic dystrophy type 1, Huntington’s disease and frontotemporal dementia/amyotrophic lateral sclerosis associated genes have been implicated in transcriptional regulation of sense gene expression, acting either at a transcriptional or posttranscriptional level. The recent evidence that antisense repeat RNAs could modulate gene expression broadens our understanding of the pathogenic pathways and adds more complexity to the development of therapeutic strategies for these disorders. In this review, we cover the amazing progress made in the understanding of the pathogenic mechanisms associated with repeat expansion neurodegenerative and neuromuscular diseases with a focus on the impact of antisense repeat transcription in the development of efficient therapies.MDPI20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/143509eng2073-442510.3390/genes11121418Castro, AFLoureiro, JRBessa, JSilveira, Iinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T12:54:02Zoai:repositorio-aberto.up.pt:10216/143509Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:29:00.175343Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries
title Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries
spellingShingle Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries
Castro, AF
Nuclear inclusions
RNA foci
Splicing misregulation
Trinucleotide repeats
title_short Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries
title_full Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries
title_fullStr Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries
title_full_unstemmed Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries
title_sort Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries
author Castro, AF
author_facet Castro, AF
Loureiro, JR
Bessa, J
Silveira, I
author_role author
author2 Loureiro, JR
Bessa, J
Silveira, I
author2_role author
author
author
dc.contributor.author.fl_str_mv Castro, AF
Loureiro, JR
Bessa, J
Silveira, I
dc.subject.por.fl_str_mv Nuclear inclusions
RNA foci
Splicing misregulation
Trinucleotide repeats
topic Nuclear inclusions
RNA foci
Splicing misregulation
Trinucleotide repeats
description Unstable repeat expansions and insertions cause more than 30 neurodegenerative and neuromuscular diseases. Remarkably, bidirectional transcription of repeat expansions has been identified in at least 14 of these diseases. More remarkably, a growing number of studies has been showing that both sense and antisense repeat RNAs are able to dysregulate important cellular pathways, contributing together to the observed clinical phenotype. Notably, antisense repeat RNAs from spinocerebellar ataxia type 7, myotonic dystrophy type 1, Huntington’s disease and frontotemporal dementia/amyotrophic lateral sclerosis associated genes have been implicated in transcriptional regulation of sense gene expression, acting either at a transcriptional or posttranscriptional level. The recent evidence that antisense repeat RNAs could modulate gene expression broadens our understanding of the pathogenic pathways and adds more complexity to the development of therapeutic strategies for these disorders. In this review, we cover the amazing progress made in the understanding of the pathogenic mechanisms associated with repeat expansion neurodegenerative and neuromuscular diseases with a focus on the impact of antisense repeat transcription in the development of efficient therapies.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/10216/143509
url https://hdl.handle.net/10216/143509
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2073-4425
10.3390/genes11121418
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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