dc.contributor.author |
Loughran, Gary |
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dc.contributor.author |
Chou, Ming-Yuan |
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dc.contributor.author |
Ivanov, Ivaylo P. |
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dc.contributor.author |
Jungreis, Irwin |
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dc.contributor.author |
Kellis, Manolis |
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dc.contributor.author |
Kiran, Anmol M. |
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dc.contributor.author |
Baranov, Pavel V. |
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dc.contributor.author |
Atkins, John F. |
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dc.date.accessioned |
2017-11-14T13:24:29Z |
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dc.date.available |
2017-11-14T13:24:29Z |
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dc.date.issued |
2014 |
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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 |
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dc.identifier.issued |
14 |
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dc.identifier.startpage |
8928 |
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dc.identifier.endpage |
8938 |
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dc.identifier.issn |
0305-1048 |
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dc.identifier.issn |
1362-4962 |
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dc.identifier.uri |
http://hdl.handle.net/10468/5016 |
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dc.identifier.doi |
10.1093/nar/gku608 |
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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. |
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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 |
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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/ |
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dc.subject |
Tobacco mosaic virus |
en |
dc.subject |
Translation termination |
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dc.subject |
Aminoglycoside antibiotics |
en |
dc.subject |
Protein synthesis |
en |
dc.subject |
Saccharomyces-cerevisiae |
en |
dc.subject |
Read through |
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dc.subject |
UGA codons |
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dc.subject |
Phenotypic suppression |
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dc.subject |
Messenger RNA |
en |
dc.subject |
Sequence |
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dc.title |
Evidence of efficient stop codon readthrough in four mammalian genes |
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dc.type |
Article (peer-reviewed) |
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dc.internal.authorcontactother |
John F. Atkins, Biochemistry, University College Cork , Cork, Ireland T: +353-21-490-3000. E: j.atkins@ucc.ie |
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dc.internal.availability |
Full text available |
en |
dc.description.version |
Published Version |
en |
dc.internal.rssid |
270208324 |
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dc.contributor.funder |
Wellcome Trust
|
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dc.contributor.funder |
National Institutes of Health
|
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dc.contributor.funder |
National Science Council
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dc.contributor.funder |
Science Foundation Ireland
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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/
|
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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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