Evidence of efficient stop codon readthrough in four mammalian genes

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dc.contributor.authorLoughran, Gary
dc.contributor.authorChou, Ming-Yuan
dc.contributor.authorIvanov, Ivaylo P.
dc.contributor.authorJungreis, Irwin
dc.contributor.authorKellis, Manolis
dc.contributor.authorKiran, Anmol M.
dc.contributor.authorBaranov, Pavel V.
dc.contributor.authorAtkins, John F.
dc.contributor.funderWellcome Trust
dc.contributor.funderNational Institutes of Health
dc.contributor.funderNational Science Council
dc.contributor.funderScience Foundation Ireland
dc.date.accessioned2017-11-14T13:24:29Z
dc.date.available2017-11-14T13:24:29Z
dc.date.issued2014
dc.description.abstractStop codon readthrough is used extensively by viruses to expand their gene expression. Until recent discoveries in Drosophila, only a very limited number of readthrough cases in chromosomal genes had been reported. Analysis of conserved protein coding signatures that extend beyond annotated stop codons identified potential stop codon readthrough of four mammalian genes. Here we use a modified targeted bioinformatic approach to identify a further three mammalian readthrough candidates. All seven genes were tested experimentally using reporter constructs transfected into HEK-293T cells. Four displayed efficient stop codon readthrough, and these have UGA immediately followed by CUAG. Comparative genomic analysis revealed that in the four readthrough candidates containing UGA-CUAG, this motif is conserved not only in mammals but throughout vertebrates with the first six of the seven nucleotides being universally conserved. The importance of the CUAG motif was confirmed using a systematic mutagenesis approach. One gene, OPRL1, encoding an opiate receptor, displayed extremely efficient levels of readthrough (similar to 31%) in HEK-293T cells. Signals both 5' and 3' of the OPRL1 stop codon contribute to this high level of readthrough. The sequence UGA-CUA alone can support 1.5% readthrough, underlying its importance.en
dc.description.sponsorshipScience Foundation Ireland (08/IN.I/B1889; 12/IP/1492); National Science Council (NSC 101-2917-I-564-049); National Institutes of Health (NIH-1-R01-HG004037-07; NSF-DBI-0644282; NIH-U41-HG007234); Wellcome Trust (094423)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLoughran, G., Chou, M.-Y., Ivanov, I. P., Jungreis, I., Kellis, M., Kiran, A. M., Baranov, P. V. and Atkins, J. F. (2014) 'Evidence of efficient stop codon readthrough in four mammalian genes', Nucleic Acids Research, 42(14), pp. 8928-8938. doi: 10.1093/nar/gku608en
dc.identifier.doi10.1093/nar/gku608
dc.identifier.endpage8938
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.issued14
dc.identifier.journaltitleNucleic Acids Researchen
dc.identifier.startpage8928
dc.identifier.urihttps://hdl.handle.net/10468/5016
dc.identifier.volume42
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IP/1492/IE/Using ribosome profiling to study translation initiation/elongation and facilitate optimization of protein synthesis/
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/gku608
dc.rights© 2014, the Authors. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectTobacco mosaic virusen
dc.subjectTranslation terminationen
dc.subjectAminoglycoside antibioticsen
dc.subjectProtein synthesisen
dc.subjectSaccharomyces-cerevisiaeen
dc.subjectRead throughen
dc.subjectUGA codonsen
dc.subjectPhenotypic suppressionen
dc.subjectMessenger RNAen
dc.subjectSequenceen
dc.titleEvidence of efficient stop codon readthrough in four mammalian genesen
dc.typeArticle (peer-reviewed)en
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