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dc.contributor.authorToribio, René
dc.contributor.authorDíaz-López, Irene
dc.contributor.authorBoskovic, Jasminka 
dc.contributor.authorVentoso, Ivan
dc.date.accessioned2018-10-23T12:17:53Z
dc.date.available2018-10-23T12:17:53Z
dc.date.issued2018-05-04
dc.identifier.citationNucleic Acids Res. 2018; 46 (8): 4176-4187.es_ES
dc.identifier.issn0305-1048es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6503
dc.description.abstractThe topology and dynamics of the scanning ribosomal 43S pre-initiation complex (PIC) bound to mRNA and initiation factors (eIFs) are probably the least understood aspects of translation initiation in eukaryotes. Recently, we described a trapping mechanism in alphavirus that stalls the PIC during scanning of viral mRNA. Using this model, we were able to snapshot for the first time the eIF4A helicase bound to mRNA in a 48S initiation complex assembled in vitro. This interaction was only detected in the presence of the natural stem loop structure (DLP) located downstream from the AUG in viral mRNA that promoted stalling of the PIC, suggesting that DLP stability was enough to jam the helicase activity of eIF4A in a fraction of assembled 48S complexes. However, a substantial proportion of DLP mRNA molecules were effectively unwound by eIF4A in vitro, an activity that alphaviruses counteract in infected cells by excluding eIF4A from viral factories. Our data indicated that eIF4A-mRNA contact occurred in (or near) the ES6S region of the 40S subunit, suggesting that incoming mRNA sequences penetrate through the ES6S region during the scanning process. We propose a topological model of the scanning PIC and how some viruses have exploited this topology to translate their mRNAs with fewer eIF requirements.es_ES
dc.description.sponsorshipWe are indebted to Jerry Pelletier (McGill University) for providing us with hippuristanol. We also thank the Genomics Facility at the López Neira Institute (Granada, Spain) for efficient analysis of toeprinting products, and the Electron Microscopy facility of the CBMSO for negative staining EM.es_ES
dc.language.isoenges_ES
dc.publisherOxford University Presses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject43S PREINITIATION COMPLEXes_ES
dc.subjectSECONDARY STRUCTUREes_ES
dc.subjectHELICASE ACTIVITYes_ES
dc.subjectCODON SELECTIONes_ES
dc.subjectFACTOR 4Aes_ES
dc.subjectFACTOR 4Ges_ES
dc.subjectEIF4Aes_ES
dc.subjectMECHANISMes_ES
dc.subjectRIBOSOMEes_ES
dc.subjectINHIBITIONes_ES
dc.titleTranslation initiation of alphavirus mRNA reveals new insights into the topology of the 48S initiation complexes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID29415133es_ES
dc.format.volume46es_ES
dc.format.number8es_ES
dc.format.page4176-4187es_ES
dc.identifier.doi10.1093/nar/gky071es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.description.peerreviewed
dc.identifier.e-issn1362-4962es_ES
dc.relation.publisherversionhttps://doi.org/10.1093/nar/gky071es_ES
dc.identifier.journalNucleic acids researches_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigaciónes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Microscopía Electrónicaes_ES
dc.relation.projectIDinfo:eu-repo/gratAgreement/ES/BFU2013-4005Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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