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

© 2014 Garcia-Moreno et al. 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 initiatio...

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Autores: García-Moreno, Manuel, Sanz, Miguel Ángel, Carrasco Llamas, Luis
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/139550
Acceso en línea:http://hdl.handle.net/10261/139550
Access Level:acceso abierto
Palabra clave:AUG selection
viral protein synthesis
Sindbis virus translation
Initiation factors
scanning mechanism
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spelling Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in sindbis virus subgenomic mRNAGarcía-Moreno, ManuelSanz, Miguel ÁngelCarrasco Llamas, LuisAUG selectionviral protein synthesisSindbis virus translationInitiation factorsscanning mechanism© 2014 Garcia-Moreno et al. 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.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 acknowledged.Peer ReviewedCold Spring Harbor Laboratory PressMinisterio de Economía y Competitividad (España)Fundación Ramón ArecesConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2016201620152016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/139550reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1395502026-05-22T06:33:51Z
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
García-Moreno, Manuel
AUG selection
viral protein synthesis
Sindbis virus translation
Initiation factors
scanning mechanism
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 García-Moreno, Manuel
Sanz, Miguel Ángel
Carrasco Llamas, Luis
author García-Moreno, Manuel
author_facet García-Moreno, Manuel
Sanz, Miguel Ángel
Carrasco Llamas, Luis
author_role author
author2 Sanz, Miguel Ángel
Carrasco Llamas, Luis
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Fundación Ramón Areces
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv AUG selection
viral protein synthesis
Sindbis virus translation
Initiation factors
scanning mechanism
topic AUG selection
viral protein synthesis
Sindbis virus translation
Initiation factors
scanning mechanism
description © 2014 Garcia-Moreno et al. 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
2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/139550
url http://hdl.handle.net/10261/139550
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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