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dc.contributor.author Dzananovic, Edis
dc.contributor.author Astha
dc.contributor.author Chojnowski, Grzegorz
dc.contributor.author Deo, Soumya
dc.contributor.author Booy, Evan P.
dc.contributor.author Padilla-Meier, Pauline
dc.contributor.author McEleney, Kevin
dc.contributor.author Bujnicki, Janusz M.
dc.contributor.author Patel, Trushar R.
dc.contributor.author McKenna, Sean A.
dc.date.accessioned 2019-04-01T02:58:29Z
dc.date.available 2019-04-01T02:58:29Z
dc.date.issued 2017
dc.identifier.citation Dzananovic, E., Astha, Chojnowsk, G., Deo, S., Booy, E. P., Padilla-Meier, P.,...McKenna, S. A. (2017). Impact of the structural integrity of the three-way junction of adenovirus VAI RNA on PKR inhibition. PloS ONE, 12(10), e0186849. .https://doi.org/10.1371/journal. pone.0186849 en_US
dc.identifier.uri https://hdl.handle.net/10133/5312
dc.description Sherpa Romeo green journal. Open access article. Creative Commons Attribution License applies. en_US
dc.description.abstract Highly structured RNA derived from viral genomes is a key cellular indicator of viral infection. In response, cells produce the interferon inducible RNA-dependent protein kinase (PKR) that, when bound to viral dsRNA, phosphorylates eukaryotic initiation factor 2αand attenuates viral protein translation. Adenovirus can evade this line of defence through transcription of a non-coding RNA, VAI, an inhibitor of PKR. VAI consists of three base-paired regions that meet at a three-way junction; an apical stem responsible for the interaction with PKR, a central stem required for inhibition, and a terminal stem. Recent studies have highlighted the potential importance of the tertiary structure of the three-way junction to PKR inhibition by enabling interaction between regions of the central and terminal stems. To further investigate the role of the three-way junction, we characterized the binding affinity and inhibitory potential of central stem mutants designed to introduce subtle alterations. These results were then correlated with small-angle X-ray scattering solution studies and computational tertiary structural models. Our results demonstrate that while mutations to the central stem have no observable effect on binding affinity to PKR, mutations that appear to disrupt the structure of the three-way junction prevent inhibition of PKR. Therefore, we propose that instead of simply sequestering PKR, a specific structural conformation of the PKR-VAI complex may be required for inhibition. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.title Impact of the structural integrity of the three-way junction of adenovirus VAI RNA on PKR inhibition en_US
dc.type Article en_US
dc.publisher.url https://dx.doi.org/10.1371/journal.pone.0186849


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