Mecanismos de iniciación de la traducción de los mRNAS del virus Sindbis
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 20-04-2015
| Autor: | |
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| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | español |
| OAI Identifier: | oai:repositorio.uam.es:10486/667536 |
| Acceso en línea: | http://hdl.handle.net/10486/667536 |
| Access Level: | acceso abierto |
| Palabra clave: | Alphavirus - Tesis doctorales Biología y Biomedicina / Biología |
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Mecanismos de iniciación de la traducción de los mRNAS del virus Sindbis |
| title |
Mecanismos de iniciación de la traducción de los mRNAS del virus Sindbis |
| spellingShingle |
Mecanismos de iniciación de la traducción de los mRNAS del virus Sindbis García Moreno, Manuel Alphavirus - Tesis doctorales Biología y Biomedicina / Biología |
| title_short |
Mecanismos de iniciación de la traducción de los mRNAS del virus Sindbis |
| title_full |
Mecanismos de iniciación de la traducción de los mRNAS del virus Sindbis |
| title_fullStr |
Mecanismos de iniciación de la traducción de los mRNAS del virus Sindbis |
| title_full_unstemmed |
Mecanismos de iniciación de la traducción de los mRNAS del virus Sindbis |
| title_sort |
Mecanismos de iniciación de la traducción de los mRNAS del virus Sindbis |
| dc.creator.none.fl_str_mv |
García Moreno, Manuel |
| author |
García Moreno, Manuel |
| author_facet |
García Moreno, Manuel |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Carrasco Llamas, Luis Sanz Fernández, Miguel Angel Departamento de Biología Molecular Facultad de Ciencias Centro de Biología Molecular Severo Ochoa (CBM) |
| dc.subject.none.fl_str_mv |
Alphavirus - Tesis doctorales Biología y Biomedicina / Biología |
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Alphavirus - Tesis doctorales Biología y Biomedicina / Biología |
| description |
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 20-04-2015 |
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2015 |
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2015 2015-04-20 |
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doctoral thesis http://purl.org/coar/resource_type/c_db06 NA http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
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info:eu-repo/semantics/doctoralThesis |
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http://hdl.handle.net/10486/667536 |
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http://hdl.handle.net/10486/667536 |
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Español spa |
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Español |
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spa |
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Mecanismos de iniciación de la traducción de los mRNAS del virus SindbisGarcía Moreno, ManuelAlphavirus - Tesis doctoralesBiología y Biomedicina / BiologíaTesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 20-04-2015Alphaviruses are responsible for a variety of diseases, including some fatal encephalitis, in humans and other vertebrates. Sindbis virus (SINV) is a representative member of alphaviruses, which contain a positive single-stranded RNA as genome. In the early phase after infection, this genomic RNA is translated following a canonical mechanism, while a subgenomic mRNA (sgmRNA) directs the synthesis of viral structural proteins during the late phase of infection, when the translation of host cellular mRNAs has been shut-off. The mechanism by which this sgmRNA is translated under these conditions has been the object of intensive research during the past few years. In the present work we demonstrate that the eukaryotic initiation factor (eIF) 4A is not required to translate SINV sgmRNA in mammalian infected cells. However, eIF4A is required for efficient translation in cells transfected with in vitro synthesized sgmRNA. Therefore, this viral mRNA exhibits a dual mechanism for its translation. In addition, other eIFs including eIF4E or PABP may not participate in this process in infected cells. Furthermore, in this viral mRNA exists a hairpin structure (DLP) that confers eIF2, but not eIF4A independence. In sharp contrast to what is observed in mammalian cells, active eIF2 is necessary to translate SINV sgmRNA in insect cells, and the DLP does not confer any translational advantage. Nevertheless, eIF4A is dispensable for SINV sgmRNA translation in mosquito cells. These findings indicate that SINV sgmRNA translation requires different initiation factors in vertebrate and insect cells. Besides, we show that the translation mechanism of this mRNA involves the scanning of the 5’ untranslated region (5’- UTR) by the preinitiation complex in both cell lines. Moreover, we have constructed some viral mRNAs bearing two AUG initiation codons that respond differentially to eIF2 inactivation, indicating that AUG selection is dependent on the cellular context, the phosphorylation state of eIF2α and the presence of regulatory elements such as DLP. Collectively, these results suggest that translation of alphavirus sgmRNA follows a novel scanning mechanism to initiate translation and to select the correct AUG initiation codon, without the participation of crucial eIFs. Finally, we found a new motif, constituted by three repeated sequences, at the 3’-UTR that are necessary for the translation of both SINV genomic and subgenomic mRNAs in insect, but not in mammalian systems. Complementary sequences at the 5’-UTR also regulate SINV mRNA translation and transcription. Thus, these SINV repeated regions constitute the first example of a motif present at the 3’- UTR that provides translatability to mRNAs from an animal virus in a cell specific manner. In addition, these findings constitute a clue to better understand, at the molecular level, the evolution of alphaviruses and other arboviruses.El trabajo presentado en esta tesis doctoral ha sido realizado mediante la concesión de la beca FPI BES-2010- 039571 del Ministerio de Economía y Competitividad. Ha sido financiado por el proyecto BFU2009-07352 otorgado por la Dirección General de Investigación Científica y Técnica, Ministerio de Economía y CompetitividadCarrasco Llamas, LuisSanz Fernández, Miguel AngelDepartamento de Biología MolecularFacultad de CienciasCentro de Biología Molecular Severo Ochoa (CBM)20152015-04-20doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/667536reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridEspañolspaopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6675362026-06-23T12:46:27Z |
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15,301603 |