Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR)
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Artigo de conferência |
Idioma: | por |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/3661 |
Resumo: | Mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates signals from the cellular nutrient- and energy-status, acting namely on the protein synthesis machinery. Due to its role in regulating protein synthesis, mTOR signaling, and consequently its deregulation, is implicated in major diseases, such as cancer. Although the regulation of mTOR gene expression is not well known, major advances are emerging regarding the regulators and effects of mTOR signaling pathway. The present work demonstrates that human mTOR transcript harbors an internal ribosome entry site (IRES) element formed by a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. In addition, it is demonstrated that IRES-dependent translation of mTOR is stimulated by hypoxia with associated eIF2α phosphorylation, in a hypoxia-inducible factor 1α (HIF1α)-independent manner. This activation status in response to translational adverse conditions parallels mTOR protein levels. Moreover, our data reveal that the IRES-dependent translation of mTOR is necessary for its ability to induce cell cycle progression into S-phase. These results suggest a novel regulatory mechanism of mTOR gene expression that integrates the protein profile rearrangement triggered by global translational inhibitory conditions. |
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Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR)Genómica Funcional e EstruturalExpressão GénicaSíntese ProteicaMammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates signals from the cellular nutrient- and energy-status, acting namely on the protein synthesis machinery. Due to its role in regulating protein synthesis, mTOR signaling, and consequently its deregulation, is implicated in major diseases, such as cancer. Although the regulation of mTOR gene expression is not well known, major advances are emerging regarding the regulators and effects of mTOR signaling pathway. The present work demonstrates that human mTOR transcript harbors an internal ribosome entry site (IRES) element formed by a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. In addition, it is demonstrated that IRES-dependent translation of mTOR is stimulated by hypoxia with associated eIF2α phosphorylation, in a hypoxia-inducible factor 1α (HIF1α)-independent manner. This activation status in response to translational adverse conditions parallels mTOR protein levels. Moreover, our data reveal that the IRES-dependent translation of mTOR is necessary for its ability to induce cell cycle progression into S-phase. These results suggest a novel regulatory mechanism of mTOR gene expression that integrates the protein profile rearrangement triggered by global translational inhibitory conditions.Repositório Científico do Instituto Nacional de SaúdeMarques-Ramos, Ana2017-12-31T01:30:10Z2015-032015-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectapplication/pdfhttp://hdl.handle.net/10400.18/3661porinfo: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:RCAAP2023-07-20T15:39:47Zoai:repositorio.insa.pt:10400.18/3661Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:38:18.091771Repositório 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 |
Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR) |
title |
Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR) |
spellingShingle |
Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR) Marques-Ramos, Ana Genómica Funcional e Estrutural Expressão Génica Síntese Proteica |
title_short |
Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR) |
title_full |
Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR) |
title_fullStr |
Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR) |
title_full_unstemmed |
Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR) |
title_sort |
Internal ribosome entry site-mediated translational regulation of mammalian target of rapamycin (mTOR) |
author |
Marques-Ramos, Ana |
author_facet |
Marques-Ramos, Ana |
author_role |
author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Marques-Ramos, Ana |
dc.subject.por.fl_str_mv |
Genómica Funcional e Estrutural Expressão Génica Síntese Proteica |
topic |
Genómica Funcional e Estrutural Expressão Génica Síntese Proteica |
description |
Mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates signals from the cellular nutrient- and energy-status, acting namely on the protein synthesis machinery. Due to its role in regulating protein synthesis, mTOR signaling, and consequently its deregulation, is implicated in major diseases, such as cancer. Although the regulation of mTOR gene expression is not well known, major advances are emerging regarding the regulators and effects of mTOR signaling pathway. The present work demonstrates that human mTOR transcript harbors an internal ribosome entry site (IRES) element formed by a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. In addition, it is demonstrated that IRES-dependent translation of mTOR is stimulated by hypoxia with associated eIF2α phosphorylation, in a hypoxia-inducible factor 1α (HIF1α)-independent manner. This activation status in response to translational adverse conditions parallels mTOR protein levels. Moreover, our data reveal that the IRES-dependent translation of mTOR is necessary for its ability to induce cell cycle progression into S-phase. These results suggest a novel regulatory mechanism of mTOR gene expression that integrates the protein profile rearrangement triggered by global translational inhibitory conditions. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-03 2015-03-01T00:00:00Z 2017-12-31T01:30:10Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/conferenceObject |
format |
conferenceObject |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/3661 |
url |
http://hdl.handle.net/10400.18/3661 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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.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 |
institution |
RCAAP |
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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132119076700160 |