Nonsense suppression therapies in human genetic diseases

Detalhes bibliográficos
Autor(a) principal: Martins-Dias, Patrícia
Data de Publicação: 2021
Outros Autores: Romão, Luísa
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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spelling 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
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv 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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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