Stimulation of stop codon readthrough: frequent presence of an extended 3' RNA structural element

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dc.contributor.authorFirth, Andrew E.
dc.contributor.authorWills, Norma M.
dc.contributor.authorGesteland, Raymond F.
dc.contributor.authorAtkins, John F.
dc.contributor.funderNational Institutes of Health
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderWellcome Trust
dc.date.accessioned2017-11-14T13:24:31Z
dc.date.available2017-11-14T13:24:31Z
dc.date.issued2011
dc.description.abstractIn Sindbis, Venezuelan equine encephalitis and related alphaviruses, the polymerase is translated as a fusion with other non-structural proteins via readthrough of a UGA stop codon. Surprisingly, earlier work reported that the signal for efficient readthrough comprises a single cytidine residue 3'-adjacent to the UGA. However, analysis of variability at synonymous sites revealed strikingly enhanced conservation within the similar to 150 nt 3'-adjacent to the UGA, and RNA folding algorithms revealed the potential for a phylogenetically conserved stem-loop structure in the same region. Mutational analysis of the predicted structure demonstrated that the stem-loop increases readthrough by up to 10-fold. The same computational analysis indicated that similar RNA structures are likely to be relevant to readthrough in certain plant virus genera, notably Furovirus, Pomovirus, Tobravirus, Pecluvirus and Benyvirus, as well as the Drosophilia gene kelch. These results suggest that 3' RNA stimulatory structures feature in a much larger proportion of readthrough cases than previously anticipated, and provide a new criterion for assessing the large number of cellular readthrough candidates that are currently being revealed by comparative sequence analysis.en
dc.description.sponsorshipWellcome Trust (088789); National Institutes of Health (R01 GM079523)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationFirth, A. E., Wills, N. M., Gesteland, R. F. and Atkins, J. F. (2011) 'Stimulation of stop codon readthrough: frequent presence of an extended 3′ RNA structural element', Nucleic Acids Research, 39(15), pp. 6679-6691. doi: 10.1093/nar/gkr224en
dc.identifier.doi10.1093/nar/gkr224
dc.identifier.endpage6691
dc.identifier.issn0305-1048
dc.identifier.issued15
dc.identifier.journaltitleNucleic Acids Researchen
dc.identifier.startpage6679
dc.identifier.urihttps://hdl.handle.net/10468/5023
dc.identifier.volume39
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/08/IN.1/B1889/IE/Altered Genetic Code Readout/
dc.relation.urihttps://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkr224
dc.rights© 2011, the Authors. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/2.5
dc.subjectMurine leukemia virusen
dc.subjectOpal termination codonen
dc.subjectRead-throughen
dc.subjectSindbis virusen
dc.subjectTranslational terminationen
dc.subjectImmediately downstreamen
dc.subjectNucleotide sequenceen
dc.subjectAphid transmissionen
dc.subjectRecoding signalsen
dc.subjectGene-expressionen
dc.titleStimulation of stop codon readthrough: frequent presence of an extended 3' RNA structural elementen
dc.typeArticle (peer-reviewed)en
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