Evidence of efficient stop codon readthrough in four mammalian genes

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dc.contributor.author Loughran, Gary
dc.contributor.author Chou, Ming-Yuan
dc.contributor.author Ivanov, Ivaylo P.
dc.contributor.author Jungreis, Irwin
dc.contributor.author Kellis, Manolis
dc.contributor.author Kiran, Anmol M.
dc.contributor.author Baranov, Pavel V.
dc.contributor.author Atkins, John F.
dc.date.accessioned 2017-11-14T13:24:29Z
dc.date.available 2017-11-14T13:24:29Z
dc.date.issued 2014
dc.identifier.citation Loughran, 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/gku608 en
dc.identifier.volume 42
dc.identifier.issued 14
dc.identifier.startpage 8928
dc.identifier.endpage 8938
dc.identifier.issn 0305-1048
dc.identifier.issn 1362-4962
dc.identifier.uri http://hdl.handle.net/10468/5016
dc.identifier.doi 10.1093/nar/gku608
dc.description.abstract Stop 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.sponsorship Science 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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Oxford University Press en
dc.relation.uri https://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.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Tobacco mosaic virus en
dc.subject Translation termination en
dc.subject Aminoglycoside antibiotics en
dc.subject Protein synthesis en
dc.subject Saccharomyces-cerevisiae en
dc.subject Read through en
dc.subject UGA codons en
dc.subject Phenotypic suppression en
dc.subject Messenger RNA en
dc.subject Sequence en
dc.title Evidence of efficient stop codon readthrough in four mammalian genes en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother John F. Atkins, Biochemistry, University College Cork , Cork, Ireland T: +353-21-490-3000. E: j.atkins@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 270208324
dc.contributor.funder Wellcome Trust
dc.contributor.funder National Institutes of Health
dc.contributor.funder National Science Council
dc.contributor.funder Science Foundation Ireland
dc.description.status Peer reviewed en
dc.identifier.journaltitle Nucleic Acids Research en
dc.internal.IRISemailaddress j.atkins@ucc.ie en
dc.relation.project info: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.project info:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/08/IN.1/B1889/IE/Altered Genetic Code Readout/


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© 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. Except where otherwise noted, this item's license is described as © 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.
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