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dc.contributor.authorToribio, René
dc.contributor.authorDíaz-López, Irene
dc.contributor.authorBoskovic, Jasminka 
dc.contributor.authorVentoso, Iván
dc.identifier.citationNucleic Acids Res. 2016;44(9):4368-80.es_ES
dc.descriptionWe are indebted to Luis Menendez′s lab for helping us with acrylamide gels for sequencing and Juanjo Berlanga andMiguel Angel Rodriguez Gabriel for their support and discussions. Institutional support from the Fundacion Ramon Areces is also acknowledged. Completion of this project took approximately 3 years and the estimated cost was 10000 , excluding salaries.es_ES
dc.description.abstractDuring translation initiation, eukaryotic initiation factor 2 (eIF2) delivers the Met-tRNA to the 40S ribosomal subunit to locate the initiation codon (AUGi) of mRNA during the scanning process. Stress-induced eIF2 phosphorylation leads to a general blockade of translation initiation and represents a key antiviral pathway in mammals. However, some viral mRNAs can initiate translation in the presence of phosphorylated eIF2 via stable RNA stem-loop structures (DLP; Downstream LooP) located in their coding sequence (CDS), which promote 43S preinitiation complex stalling on the initiation codon. We show here that during the scanning process, DLPs of Alphavirus mRNA become trapped in ES6S region (680-914 nt) of 18S rRNA that are projected from the solvent side of 40S subunit. This trapping can lock the progress of the 40S subunit on the mRNA in a way that places the upstream initiator AUGi on the P site of 40S subunit, obviating the participation of eIF2. Notably, the DLP structure is released from 18S rRNA upon 60S ribosomal subunit joining, suggesting conformational changes in ES6Ss during the initiation process. These novel findings illustrate how viral mRNA is threaded into the 40S subunit during the scanning process, exploiting the topology of the 40S subunit solvent side to enhance its translation in vertebrate hosts.es_ES
dc.publisherOxford University Press es_ES
dc.subject.meshAedes es_ES
dc.subject.meshAlphavirus es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBase Sequence es_ES
dc.subject.meshCell Line es_ES
dc.subject.meshCodon, Initiator es_ES
dc.subject.meshCricetinae es_ES
dc.subject.meshGene Expression Regulation, Viral es_ES
dc.subject.meshInverted Repeat Sequences es_ES
dc.subject.meshModels, Moleculares_ES
dc.subject.meshRNA Stability es_ES
dc.subject.meshRNA, Messenger es_ES
dc.subject.meshRNA, Ribosomal, 18S es_ES
dc.subject.meshRNA, Viral es_ES
dc.subject.meshRibosomes es_ES
dc.subject.meshPeptide Chain Initiation, Translational es_ES
dc.titleAn RNA trapping mechanism in Alphavirus mRNA promotes ribosome stalling and translation initiationes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.relation.publisherversion 10.1093/nar/gkw172.es_ES
dc.identifier.journalNucleic acids researches_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Microscopía Electrónicaes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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