The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation
Autor(a) principal: | |
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Data de Publicação: | 2009 |
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/10773/27659 |
Resumo: | Translation fidelity is critical for protein synthesis and to ensure correct cell functioning. Mutations in the protein synthesis machinery or environmental factors that increase synthesis of mistranslated proteins result in cell death and degeneration and are associated with neurodegenerative diseases, cancer and with an increasing number of mitochondrial disorders. Remarkably, mRNA mistranslation plays critical roles in the evolution of the genetic code, can be beneficial under stress conditions in yeast and in Escherichia coli and is an important source of peptides for MHC class I complex in dendritic cells. Despite this, its biology has been overlooked over the years due to technical difficulties in its detection and quantification. In order to shed new light on the biological relevance of mistranslation we have generated codon misreading in Saccharomyces cerevisiae using drugs and tRNA engineering methodologies. Surprisingly, such mistranslation up-regulated the longevity gene PNC1. Similar results were also obtained in cells grown in the presence of amino acid analogues that promote protein misfolding. The overall data showed that PNC1 is a biomarker of mRNA mistranslation and protein misfolding and that PNC1-GFP fusions can be used to monitor these two important biological phenomena in vivo in an easy manner, thus opening new avenues to understand their biological relevance. |
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The yeast PNC1 longevity gene is up-regulated by mRNA mistranslationTranslation fidelity is critical for protein synthesis and to ensure correct cell functioning. Mutations in the protein synthesis machinery or environmental factors that increase synthesis of mistranslated proteins result in cell death and degeneration and are associated with neurodegenerative diseases, cancer and with an increasing number of mitochondrial disorders. Remarkably, mRNA mistranslation plays critical roles in the evolution of the genetic code, can be beneficial under stress conditions in yeast and in Escherichia coli and is an important source of peptides for MHC class I complex in dendritic cells. Despite this, its biology has been overlooked over the years due to technical difficulties in its detection and quantification. In order to shed new light on the biological relevance of mistranslation we have generated codon misreading in Saccharomyces cerevisiae using drugs and tRNA engineering methodologies. Surprisingly, such mistranslation up-regulated the longevity gene PNC1. Similar results were also obtained in cells grown in the presence of amino acid analogues that promote protein misfolding. The overall data showed that PNC1 is a biomarker of mRNA mistranslation and protein misfolding and that PNC1-GFP fusions can be used to monitor these two important biological phenomena in vivo in an easy manner, thus opening new avenues to understand their biological relevance.Public Library of Science2020-02-26T12:40:17Z2009-01-01T00:00:00Z2009info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/27659eng10.1371/journal.pone.0005212Silva, Raquel M.Duarte, Iven C. N.Paredes, João A.Lima-Costa, TatianaPerrot, MichelBoucherie, HélianGoodfellow, Brian J.Gomes, Ana C.Mateus, Denisa D.Moura, Gabriela R.Santos, Manuel A. S.info: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:RCAAP2024-02-22T11:53:35Zoai:ria.ua.pt:10773/27659Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:00:23.009591Repositório 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 |
The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation |
title |
The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation |
spellingShingle |
The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation Silva, Raquel M. |
title_short |
The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation |
title_full |
The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation |
title_fullStr |
The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation |
title_full_unstemmed |
The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation |
title_sort |
The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation |
author |
Silva, Raquel M. |
author_facet |
Silva, Raquel M. Duarte, Iven C. N. Paredes, João A. Lima-Costa, Tatiana Perrot, Michel Boucherie, Hélian Goodfellow, Brian J. Gomes, Ana C. Mateus, Denisa D. Moura, Gabriela R. Santos, Manuel A. S. |
author_role |
author |
author2 |
Duarte, Iven C. N. Paredes, João A. Lima-Costa, Tatiana Perrot, Michel Boucherie, Hélian Goodfellow, Brian J. Gomes, Ana C. Mateus, Denisa D. Moura, Gabriela R. Santos, Manuel A. S. |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Silva, Raquel M. Duarte, Iven C. N. Paredes, João A. Lima-Costa, Tatiana Perrot, Michel Boucherie, Hélian Goodfellow, Brian J. Gomes, Ana C. Mateus, Denisa D. Moura, Gabriela R. Santos, Manuel A. S. |
description |
Translation fidelity is critical for protein synthesis and to ensure correct cell functioning. Mutations in the protein synthesis machinery or environmental factors that increase synthesis of mistranslated proteins result in cell death and degeneration and are associated with neurodegenerative diseases, cancer and with an increasing number of mitochondrial disorders. Remarkably, mRNA mistranslation plays critical roles in the evolution of the genetic code, can be beneficial under stress conditions in yeast and in Escherichia coli and is an important source of peptides for MHC class I complex in dendritic cells. Despite this, its biology has been overlooked over the years due to technical difficulties in its detection and quantification. In order to shed new light on the biological relevance of mistranslation we have generated codon misreading in Saccharomyces cerevisiae using drugs and tRNA engineering methodologies. Surprisingly, such mistranslation up-regulated the longevity gene PNC1. Similar results were also obtained in cells grown in the presence of amino acid analogues that promote protein misfolding. The overall data showed that PNC1 is a biomarker of mRNA mistranslation and protein misfolding and that PNC1-GFP fusions can be used to monitor these two important biological phenomena in vivo in an easy manner, thus opening new avenues to understand their biological relevance. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-01-01T00:00:00Z 2009 2020-02-26T12:40:17Z |
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/10773/27659 |
url |
http://hdl.handle.net/10773/27659 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1371/journal.pone.0005212 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
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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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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1799137659466022912 |