Nonsense suppression therapies in human genetic diseases
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/7942 |
Resumo: | Review |
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Nonsense suppression therapies in human genetic diseasesNonsense MutationPremature Termination Codon (PTC)Readthrough TherapyStop Codon ReadthroughTranslation TerminationDoenças GenéticasGenómica FuncionalGenómica Funcional e EstruturalReviewAbout 11% of all human disease-associated gene lesions are nonsense mutations, resulting in the introduction of an in-frame premature translation-termination codon (PTC) into the protein-coding gene sequence. When translated, PTC-containing mRNAs originate truncated and often dysfunctional proteins that might be non-functional or have gain-of-function or dominant-negative effects. Therapeutic strategies aimed at suppressing PTCs to restore deficient protein function—the so-called nonsense suppression (or PTC readthrough) therapies—have the potential to provide a therapeutic benefit for many patients and in a broad range of genetic disorders, including cancer. These therapeutic approaches comprise the use of translational readthrough-inducing compounds that make the translational machinery recode an in-frame PTC into a sense codon. However, most of the mRNAs carrying a PTC can be rapidly degraded by the surveillance mechanism of nonsense-mediated decay (NMD), thus decreasing the levels of PTC-containing mRNAs in the cell and their availability for PTC readthrough. Accordingly, the use of NMD inhibitors, or readthrough-compound potentiators, may enhance the efficiency of PTC suppression. Here, we review the mechanisms of PTC readthrough and their regulation, as well as the recent advances in the development of novel approaches for PTC suppression, and their role in personalized medicine.This work was partially supported by UID/MULTI/04046/2019 Research Unit Grant (to BioISI) and by PTFC/BIM-MEC/3749/2014 research Grant (to LR) from Fundação para a Ciência e a Tecnologia, Portugal.Springer/ Birkhäuser VerlagRepositório Científico do Instituto Nacional de SaúdeMartins-Dias, PatríciaRomão, Luísa2022-02-07T16:31:31Z2021-03-222021-03-22T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/7942engCell Mol Life Sci. 2021 May;78(10):4677-4701. doi: 10.1007/s00018-021-03809-7. Epub 2021 Mar 22. Review1420-682X10.1007/s00018-021-03809-7info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:42:21Zoai:repositorio.insa.pt:10400.18/7942Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:42:43.543768Repositório 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 |
Nonsense suppression therapies in human genetic diseases |
title |
Nonsense suppression therapies in human genetic diseases |
spellingShingle |
Nonsense suppression therapies in human genetic diseases Martins-Dias, Patrícia Nonsense Mutation Premature Termination Codon (PTC) Readthrough Therapy Stop Codon Readthrough Translation Termination Doenças Genéticas Genómica Funcional Genómica Funcional e Estrutural |
title_short |
Nonsense suppression therapies in human genetic diseases |
title_full |
Nonsense suppression therapies in human genetic diseases |
title_fullStr |
Nonsense suppression therapies in human genetic diseases |
title_full_unstemmed |
Nonsense suppression therapies in human genetic diseases |
title_sort |
Nonsense suppression therapies in human genetic diseases |
author |
Martins-Dias, Patrícia |
author_facet |
Martins-Dias, Patrícia Romão, Luísa |
author_role |
author |
author2 |
Romão, Luísa |
author2_role |
author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Martins-Dias, Patrícia Romão, Luísa |
dc.subject.por.fl_str_mv |
Nonsense Mutation Premature Termination Codon (PTC) Readthrough Therapy Stop Codon Readthrough Translation Termination Doenças Genéticas Genómica Funcional Genómica Funcional e Estrutural |
topic |
Nonsense Mutation Premature Termination Codon (PTC) Readthrough Therapy Stop Codon Readthrough Translation Termination Doenças Genéticas Genómica Funcional Genómica Funcional e Estrutural |
description |
Review |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-03-22 2021-03-22T00:00:00Z 2022-02-07T16:31:31Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/7942 |
url |
http://hdl.handle.net/10400.18/7942 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cell Mol Life Sci. 2021 May;78(10):4677-4701. doi: 10.1007/s00018-021-03809-7. Epub 2021 Mar 22. Review 1420-682X 10.1007/s00018-021-03809-7 |
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info:eu-repo/semantics/embargoedAccess |
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embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Springer/ Birkhäuser Verlag |
publisher.none.fl_str_mv |
Springer/ Birkhäuser Verlag |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132173628866560 |