294 research outputs found

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

    Get PDF
    © 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 Reviewe

    Inhibition of host protein synthesis by Sindbis virus: Correlation with viral RNA replication and release of nuclear proteins to the cytoplasm

    Get PDF
    © 2014 John Wiley & Sons Ltd. Infection of mammalian cells by Sindbis virus (SINV) profoundly blocks cellular mRNA translation. Experimental evidence points to viral non-structural proteins (nsPs), in particular nsP2, as the mediator of this inhibition. However, individual expression of nsP1, nsP2, nsP3 or nsP1-4 does not block cellular protein synthesis in BHK cells. Trans-complementation of a defective SINV replicon lacking most of the coding region for nsPs by the co-expression of nsP1-4 propitiates viral RNA replication at low levels, and inhibition of cellular translation is not observed. Exit of nuclear proteins including T-cell intracellular antigen and polypyrimidine tract-binding protein is clearly detected in SINV-infected cells, but not upon the expression of nsPs, even when the defective replicon was complemented. Analysis of a SINV variant with a point mutation in nsP2, exhibiting defects in the shut-off of host protein synthesis, indicates that both viral RNA replication and the release of nuclear proteins to the cytoplasm are greatly inhibited. Furthermore, nucleoside analogues that inhibit cellular and viral RNA synthesis impede the blockade of host mRNA translation, in addition to the release of nuclear proteins. Prevention of the shut-off of host mRNA translation by nucleoside analogues is not due to the inhibition of eIF2α phosphorylation, as this prevention is also observed in PKR-/- mouse embryonic fibroblasts that do not phosphorylate eIF2α after SINV infection. Collectively, our observations are consistent with the concept that for the inhibition of cellular protein synthesis to occur, viral RNA replication must take place at control levels, leading to the release of nuclear proteins to the cytoplasm.DGICYT (Dirección General de Investigación Científica y Técnica. Ministerio de Economía y Competitividad, Spain) grant (BFU2012-31861). Fundación Ramón ArecesPeer Reviewe

    Microalgal and nitrogen-fixing bacterial consortia: from interaction to biotechnological potential

    Get PDF
    Microalgae are used in various biotechnological processes, such as biofuel production due to their high biomass yields, agriculture as biofertilizers, production of high-value-added products, decontamination of wastewater, or as biological models for carbon sequestration. The number of these biotechnological applications is increasing, and as such, any advances that contribute to reducing costs and increasing economic profitability can have a significant impact. Nitrogen fixing organisms, often called diazotroph, also have great biotechnological potential, mainly in agriculture as an alternative to chemical fertilizers. Microbial consortia typically perform more complex tasks than monocultures and can execute functions that are challenging or even impossible for individual strains or species. Interestingly, microalgae and diazotrophic organisms are capable to embrace different types of symbiotic associations. Certain corals and lichens exhibit this symbiotic relationship in nature, which enhances their fitness. However, this relationship can also be artificially created in laboratory conditions with the objective of enhancing some of the biotechnological processes that each organism carries out independently. As a result, the utilization of microalgae and diazotrophic organisms in consortia is garnering significant interest as a potential alternative for reducing production costs and increasing yields of microalgae biomass, as well as for producing derived products and serving biotechnological purposes. This review makes an effort to examine the associations of microalgae and diazotrophic organisms, with the aim of highlighting the potential of these associations in improving various biotechnological processes

    Sentencia del Tribunal de Justicia de la Unión Europea (Sala Tercera), de 20 de octubre de 2022: Plazos de pago en la contratación pública

    Get PDF
    [ES] La Sentencia del Tribunal de Justicia de la Unión Europea de 20 de octubre de 2022 (Sala Tercera, eCli:eu:C:2022:806), objeto del presente comentario, tiene una enorme relevancia para el Derecho español de la contratación pública, bloque normativo del Derecho administrativo progresivamente europeizado, en tanto que supone la quiebra del régimen de plazos de pago del precio de los contratos públicos legalmente establecid

    La colocación de la bandera LGTBI en edificios públicos: una mirada jurídica

    Get PDF
    [ES] La diversidad cultural, enriquecedora de valores y capacidades para la humanidad, como destaca el Convenio sobre la Diversidad Cultural de la UNESCO (2005), precisa de una necesaria gestión intercultural para garantizar la interacción equitativa de culturas y la posibilidad de generar expresiones culturales compartidas, adquiridas por medio del diálogo y de una actitud de respeto mutuo.Esta obra colectiva e interdisciplinar, a la que han contribuido investigadores procedentes de diversos países e instituciones, aborda la interculturalidad desde la perspectiva del respeto y la promoción de los Derechos Humanos. De este modo, se tratan las políticas públicas y la tutela judicial de la interculturalidad, afrontando la discriminación y odio vinculados a la cultura, el uso del Derecho Penal como elemento represor de la diferencia, los conflictos territoriales y la protección frente a la discriminación en el ámbito laboral. Así mismo, se presta especial atención a los colectivos vulnerables, la integración de segundas y posteriores generaciones y a los modelos de intervención para la convivencia intercultural, destacando la diversidad cultural en el contexto educativo y las diferentes estrategias comunicativas. Todo ello, sin olvidar el análisis desde una perspectiva cuantitativa de la interculturalidad y los Derechos Humanos y su abordaje crítico desde el enfoque interseccional

    La morosidad de la administración: obligaciones y contratos públicos

    Get PDF
    [ES]El estudio de la morosidad de la Administración plantea la necesidad de formular un concepto de obligación administrativa. En la presente investigación se delimitan los conceptos de obligación, deber, inactividad, morosidad y mora de la Administración. Asimismo, se analizan los problemas y avances normativos relacionados la morosidad en diversos ámbitos: las prestaciones sanitarias, las obligaciones económicas de la Junta de Andalucía, los conciertos farmacéuticos, el servicio de asistencia jurídica gratuita, las becas y ayudas al estudio, el sistema de atención a la dependencia y la situación de los ERTE tras la crisis de la COVID-19

    Juan José Rastrollo Suárez, Crisis, reacción y evolución: el teletrabajo en el sector público

    Get PDF
    Recensión del libro de Juan José Rastrollo Suárez, Crisis, reacción y evolución: el teletrabajo en el sector público, Thomson Reuters Aranzadi, 2021, 183 pp
    corecore