Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innata

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 30-04-2015

Detalhes bibliográficos
Autor: Márquez Jurado, Silvia
Tipo de documento: tese
Data de publicação:2015
País:España
Recursos:Universidad Autónoma de Madrid
Repositório:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:espanhol
inglês
OAI Identifier:oai:repositorio.uam.es:10486/667972
Acesso em linha:http://hdl.handle.net/10486/667972
Access Level:Acceso aberto
Palavra-chave:Reacción inmunitaria - Tesis doctoral
Biología y Biomedicina / Biología
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repository_id_str
dc.title.none.fl_str_mv Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innata
title Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innata
spellingShingle Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innata
Márquez Jurado, Silvia
Reacción inmunitaria - Tesis doctoral
Biología y Biomedicina / Biología
title_short Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innata
title_full Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innata
title_fullStr Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innata
title_full_unstemmed Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innata
title_sort Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innata
dc.creator.none.fl_str_mv Márquez Jurado, Silvia
author Márquez Jurado, Silvia
author_facet Márquez Jurado, Silvia
author_role author
dc.contributor.none.fl_str_mv Almazán Toral, Fernando
Enjuanes Sánchez, Luis
Departamento de Biología Molecular
Facultad de Ciencias
CSIC. Centro Nacional de Biotecnología (CNB)
dc.subject.none.fl_str_mv Reacción inmunitaria - Tesis doctoral
Biología y Biomedicina / Biología
topic Reacción inmunitaria - Tesis doctoral
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: 30-04-2015
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-04-30
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/667972
url http://hdl.handle.net/10486/667972
dc.language.none.fl_str_mv Español
spa
Inglés
eng
language_invalid_str_mv Español
Inglés
language spa
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.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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spelling Identificación y caracterización de un motivo de RNA similar al elemento GAIT en el extremo 3' del genoma del TGEV que modula la respuesta inmune innataMárquez Jurado, SilviaReacción inmunitaria - Tesis doctoralBiología y Biomedicina / BiologíaTesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 30-04-2015Coronaviruses (CoVs) are enveloped, positive-sense RNA viruses that belong to the order Nidovirales, causing respiratory and enteric infections in a wide range of animals and human. CoV replication and transcription take place at cytoplasmic double membrane vesicles and is mediated by the viral replicase. These processes require the specific recognition of RNA cis-acting signals located at the ends of the viral genome. Similarly to many other RNA viruses, the virus-encoded replication complex presumably associates with host-cell proteins to complete the synthesis of viral RNA. Using transmissible gastroenteritis coronavirus (TGEV) as a model, we previously identified nine cellular proteins interacting with the genome 3’ end, including the heterogeneous nuclear ribonucleoproteins (hnRNPs) A0, A1, A2/B1, Q and U, the translational factors glutamyl-prolyl-tRNA synthetase (EPRS), arginyl-tRNA synthetase (RRS) and poly(A)-binding protein (PABP), and the p100 transcriptional coactivator. From these proteins, a functional role on viral RNA synthesis was reported for hnRNP Q, EPRS and PABP. In this thesis, the functional study was extended to the proteins RRS and p100, and a positive role of both cell proteins in the viral RNA synthesis was demonstrated by silencing analysis. The RNA domains interacting with the cell proteins involved in TGEV RNA synthesis were further analyzed to study their mechanisms of action. After several RNA mapping stages, a 32-nt RNA motif located at the 3’ end of the TGEV genome was found to specifically interact with EPRS and RRS. This interaction was also observed during the infection, where both tRNA synthetases specifically interacted with the viral genomic and subgenomic RNAs. Interestingly, both aminoacil tRNA synthetases were incorporated into the viral particle, possibly through their interaction with the viral genome RNA. This RNA motif presented high homology in sequence and secondary structure with the gamma interferon activated inhibitor of translation (GAIT) element, which is present at the 3’ end of several mRNAs coding proinflammatory proteins. The GAIT element is involved in the translation silencing of these mRNAs through its interaction with the GAIT complex [EPRS, hnRNP Q, L13a, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)] to favor the resolution of inflammation. Similarly to the cellular GAIT element, the viral RNA domain was able to bind the GAIT complex and inhibit the in vitro translation of a chimeric mRNA containing this motif, suggesting that the viral RNA domain could constitute the first GAIT-like motif described in a positive RNA virus. To test the functional role of the GAIT-like motif in TGEV infection, two recombinant viruses harboring mutations in this motif were engineered and characterized. Abrogation of the GAIT-like motif did not affect virus growth in cell cultures. However, an exacerbated innate immune response, mediated by the melanoma differentiation-associated gene 5 (MDA5) pathway, was observed in cells infected with the mutant viruses compared with the parental virus infection. Furthermore, mutant viruses were more sensitive to interferon beta than the parental virus. Altogether, these data suggested that the GAIT-like motif modulates the host innate immune response.Almazán Toral, FernandoEnjuanes Sánchez, LuisDepartamento de Biología MolecularFacultad de CienciasCSIC. Centro Nacional de Biotecnología (CNB)20152015-04-30doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/667972reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridEspañolspaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6679722026-06-23T12:46:27Z
score 15,300719

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