More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer
Autor(a) principal: | |
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Data de Publicação: | 2016 |
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/10400.18/4394 |
Resumo: | The scanning model for eukaryotic mRNA translation initiation states that the small ribosomal subunit, along with initiation factors, binds at the cap structure at the 5' end of the mRNA and scans the 5' untranslated region (5'UTR) until an initiation codon is found. However, under conditions that impair canonical cap-dependent translation, the synthesis of some proteins is kept by alternative mechanisms that are required for cell survival and stress recovery. Alternative modes of translation initiation include cap- and/or scanning-independent mechanisms of ribosomal recruitment. In most cap-independent translation initiation events there is a direct recruitment of the 40S ribosome into a position upstream, or directly at, the initiation codon via a specific internal ribosome entry site (IRES) element in the 5'UTR. Yet, in some cellular mRNAs, a different translation initiation mechanism that is neither cap- nor IRES-dependent seems to occur through a special RNA structure called cap-independent translational enhancer (CITE). Recent evidence uncovered a distinct mechanism through which mRNAs containing N 6-methyladenosine (m6A) residues in their 5'UTR directly bind eukaryotic initiation factor 3 (eIF3) and the 40S ribosomal subunit in order to initiate translation in the absence of the cap-binding proteins. This review focuses on the important role of cap-independent translation mechanisms in human cells and how these alternative mechanisms can either act individually or cooperate with other cis-acting RNA regulons to orchestrate specific translational responses triggered upon several cellular stress states, and diseases such as cancer. Elucidation of these non-canonical mechanisms reveals the complexity of translational control and points out their potential as prospective novel therapeutic targets. |
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More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancerCancerCellular StressCis-acting RNA RegulonsDiseaseEukaryotic Translation InitiationNon-canonical Translation InitiationRepression of Global Protein SynthesisExpressão GénicaGenómica Funcional e EstruturalThe scanning model for eukaryotic mRNA translation initiation states that the small ribosomal subunit, along with initiation factors, binds at the cap structure at the 5' end of the mRNA and scans the 5' untranslated region (5'UTR) until an initiation codon is found. However, under conditions that impair canonical cap-dependent translation, the synthesis of some proteins is kept by alternative mechanisms that are required for cell survival and stress recovery. Alternative modes of translation initiation include cap- and/or scanning-independent mechanisms of ribosomal recruitment. In most cap-independent translation initiation events there is a direct recruitment of the 40S ribosome into a position upstream, or directly at, the initiation codon via a specific internal ribosome entry site (IRES) element in the 5'UTR. Yet, in some cellular mRNAs, a different translation initiation mechanism that is neither cap- nor IRES-dependent seems to occur through a special RNA structure called cap-independent translational enhancer (CITE). Recent evidence uncovered a distinct mechanism through which mRNAs containing N 6-methyladenosine (m6A) residues in their 5'UTR directly bind eukaryotic initiation factor 3 (eIF3) and the 40S ribosomal subunit in order to initiate translation in the absence of the cap-binding proteins. This review focuses on the important role of cap-independent translation mechanisms in human cells and how these alternative mechanisms can either act individually or cooperate with other cis-acting RNA regulons to orchestrate specific translational responses triggered upon several cellular stress states, and diseases such as cancer. Elucidation of these non-canonical mechanisms reveals the complexity of translational control and points out their potential as prospective novel therapeutic targets.This work was partially supported by Fundação para a Ciência e a Tecnologia (UID/MULTI/04046/2013 to BioISI from FCT/MCTES/PIDDAC). Rafaela Lacerda and Juliane Menezes were supported by fellowships from Fundação para a Ciência e a Tecnologia (SFRH/BD/74778/2010 and SFRH/BPD/98360/2013, respectively).Springer Verlag/Birkhäuser BaselRepositório Científico do Instituto Nacional de SaúdeLacerda, RafaelaMenezes, JulianeRomão, Luísa2017-03-02T12:45:49Z2016-12-022016-12-02T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/4394engell Mol Life Sci. 2017 May;74(9):1659-1680. doi: 10.1007/s00018-016-2428-2. Epub 2016 Dec 2.1420-682X10.1007/s00018-016-2428-2info: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:RCAAP2023-07-20T15:40:14Zoai:repositorio.insa.pt:10400.18/4394Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:39:02.273166Repositório 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 |
More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer |
title |
More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer |
spellingShingle |
More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer Lacerda, Rafaela Cancer Cellular Stress Cis-acting RNA Regulons Disease Eukaryotic Translation Initiation Non-canonical Translation Initiation Repression of Global Protein Synthesis Expressão Génica Genómica Funcional e Estrutural |
title_short |
More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer |
title_full |
More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer |
title_fullStr |
More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer |
title_full_unstemmed |
More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer |
title_sort |
More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer |
author |
Lacerda, Rafaela |
author_facet |
Lacerda, Rafaela Menezes, Juliane Romão, Luísa |
author_role |
author |
author2 |
Menezes, Juliane Romão, Luísa |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Lacerda, Rafaela Menezes, Juliane Romão, Luísa |
dc.subject.por.fl_str_mv |
Cancer Cellular Stress Cis-acting RNA Regulons Disease Eukaryotic Translation Initiation Non-canonical Translation Initiation Repression of Global Protein Synthesis Expressão Génica Genómica Funcional e Estrutural |
topic |
Cancer Cellular Stress Cis-acting RNA Regulons Disease Eukaryotic Translation Initiation Non-canonical Translation Initiation Repression of Global Protein Synthesis Expressão Génica Genómica Funcional e Estrutural |
description |
The scanning model for eukaryotic mRNA translation initiation states that the small ribosomal subunit, along with initiation factors, binds at the cap structure at the 5' end of the mRNA and scans the 5' untranslated region (5'UTR) until an initiation codon is found. However, under conditions that impair canonical cap-dependent translation, the synthesis of some proteins is kept by alternative mechanisms that are required for cell survival and stress recovery. Alternative modes of translation initiation include cap- and/or scanning-independent mechanisms of ribosomal recruitment. In most cap-independent translation initiation events there is a direct recruitment of the 40S ribosome into a position upstream, or directly at, the initiation codon via a specific internal ribosome entry site (IRES) element in the 5'UTR. Yet, in some cellular mRNAs, a different translation initiation mechanism that is neither cap- nor IRES-dependent seems to occur through a special RNA structure called cap-independent translational enhancer (CITE). Recent evidence uncovered a distinct mechanism through which mRNAs containing N 6-methyladenosine (m6A) residues in their 5'UTR directly bind eukaryotic initiation factor 3 (eIF3) and the 40S ribosomal subunit in order to initiate translation in the absence of the cap-binding proteins. This review focuses on the important role of cap-independent translation mechanisms in human cells and how these alternative mechanisms can either act individually or cooperate with other cis-acting RNA regulons to orchestrate specific translational responses triggered upon several cellular stress states, and diseases such as cancer. Elucidation of these non-canonical mechanisms reveals the complexity of translational control and points out their potential as prospective novel therapeutic targets. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12-02 2016-12-02T00:00:00Z 2017-03-02T12:45:49Z |
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/10400.18/4394 |
url |
http://hdl.handle.net/10400.18/4394 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
ell Mol Life Sci. 2017 May;74(9):1659-1680. doi: 10.1007/s00018-016-2428-2. Epub 2016 Dec 2. 1420-682X 10.1007/s00018-016-2428-2 |
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 Verlag/Birkhäuser Basel |
publisher.none.fl_str_mv |
Springer Verlag/Birkhäuser Basel |
dc.source.none.fl_str_mv |
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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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