Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNA

Translation initiation of alphavirus subgenomic mRNA (sgmRNA) can occur in the absence of several initiation factors (eIFs) in infected cells; however, the precise translation mechanism is still poorly understood. In this study, we have examined the mechanism of initiation and AUG selection in Sindb...

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Detalhes bibliográficos
Autores: Garcia-Moreno, M., Sanz, Miguel Angel, Carrasco, L.
Formato: artículo
Fecha de publicación:2015
País:España
Recursos:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/672903
Acesso em linha:http://hdl.handle.net/10486/672903
https://dx.doi.org/10.1261/rna.047084.114
Access Level:acceso abierto
Palavra-chave:AUG selection
Initiation factors
Scanning mechanism
Sindbis virus translation
Viral protein synthesis
Biología y Biomedicina / Biología
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spelling Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNAGarcia-Moreno, M.Sanz, Miguel AngelCarrasco, L.AUG selectionInitiation factorsScanning mechanismSindbis virus translationViral protein synthesisBiología y Biomedicina / BiologíaTranslation initiation of alphavirus subgenomic mRNA (sgmRNA) can occur in the absence of several initiation factors (eIFs) in infected cells; however, the precise translation mechanism is still poorly understood. In this study, we have examined the mechanism of initiation and AUG selection in Sindbis virus (SINV) sgmRNA. Our present findings suggest that sgmRNA is translated via a scanning mechanism, since the presence of a hairpin structure before the initiation codon hampers protein synthesis directed by this mRNA. In addition, translation is partially recovered when an in-frame AUG codon is placed upstream of this hairpin. This scanning process takes place without the participation of eIF4A and active eIF2. These results, combined with our findings through modifying the SINV sgmRNA leader sequence, do not support the possibility of a direct initiation from the start codon without previous scanning, or a shunting mechanism. Moreover, studies carried out with sgmRNAs containing two alternative AUG codons within a good context for translation reveal differences in AUG selection which are dependent on the cellular context and the phosphorylation state of eIF2α. Thus, initiation at the additional AUG is strictly dependent on active eIF2, whereas the genuine AUG codon can start translation following eIF2α inactivation. Collectively, our results suggest that SINV sgmRNA is translated by a scanning mechanism without the potential participation of crucial eIFs. A model is presented that explains the mechanism of initiation of mRNAs bearing two alternative initiation codonsThis work was supported by a DGICYT (Dirección General de Investigación Científica y Técnica. Ministerio de Economía y Competitividad, Spain) grant BFU2012-31861. M.G.-M. is holder of a FPI (Formación de Personal Investigador) fellowship. The Institutional Grant awarded to the Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM) by the Fundación Ramón Areces is acknowledgedCold Spring Harbor Laboratory PressDepartamento de Biología MolecularFacultad de Ciencias20152015-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/672903https://dx.doi.org/10.1261/rna.047084.114reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6729032026-06-23T12:46:27Z
dc.title.none.fl_str_mv Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNA
title Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNA
spellingShingle Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNA
Garcia-Moreno, M.
AUG selection
Initiation factors
Scanning mechanism
Sindbis virus translation
Viral protein synthesis
Biología y Biomedicina / Biología
title_short Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNA
title_full Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNA
title_fullStr Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNA
title_full_unstemmed Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNA
title_sort Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNA
dc.creator.none.fl_str_mv Garcia-Moreno, M.
Sanz, Miguel Angel
Carrasco, L.
author Garcia-Moreno, M.
author_facet Garcia-Moreno, M.
Sanz, Miguel Angel
Carrasco, L.
author_role author
author2 Sanz, Miguel Angel
Carrasco, L.
author2_role author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv AUG selection
Initiation factors
Scanning mechanism
Sindbis virus translation
Viral protein synthesis
Biología y Biomedicina / Biología
topic AUG selection
Initiation factors
Scanning mechanism
Sindbis virus translation
Viral protein synthesis
Biología y Biomedicina / Biología
description Translation initiation of alphavirus subgenomic mRNA (sgmRNA) can occur in the absence of several initiation factors (eIFs) in infected cells; however, the precise translation mechanism is still poorly understood. In this study, we have examined the mechanism of initiation and AUG selection in Sindbis virus (SINV) sgmRNA. Our present findings suggest that sgmRNA is translated via a scanning mechanism, since the presence of a hairpin structure before the initiation codon hampers protein synthesis directed by this mRNA. In addition, translation is partially recovered when an in-frame AUG codon is placed upstream of this hairpin. This scanning process takes place without the participation of eIF4A and active eIF2. These results, combined with our findings through modifying the SINV sgmRNA leader sequence, do not support the possibility of a direct initiation from the start codon without previous scanning, or a shunting mechanism. Moreover, studies carried out with sgmRNAs containing two alternative AUG codons within a good context for translation reveal differences in AUG selection which are dependent on the cellular context and the phosphorylation state of eIF2α. Thus, initiation at the additional AUG is strictly dependent on active eIF2, whereas the genuine AUG codon can start translation following eIF2α inactivation. Collectively, our results suggest that SINV sgmRNA is translated by a scanning mechanism without the potential participation of crucial eIFs. A model is presented that explains the mechanism of initiation of mRNAs bearing two alternative initiation codons
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/672903
https://dx.doi.org/10.1261/rna.047084.114
url http://hdl.handle.net/10486/672903
https://dx.doi.org/10.1261/rna.047084.114
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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