Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences

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dc.contributor.author Ivanov, Ivaylo P.
dc.contributor.author Firth, Andrew E.
dc.contributor.author Michel, Audrey M.
dc.contributor.author Atkins, John F.
dc.contributor.author Baranov, Pavel V.
dc.date.accessioned 2017-11-14T13:24:31Z
dc.date.available 2017-11-14T13:24:31Z
dc.date.issued 2011
dc.identifier.citation Ivanov, I. P., Firth, A. E., Michel, A. M., Atkins, J. F. and Baranov, P. V. (2011) 'Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences', Nucleic Acids Research, 39(10), pp. 4220-4234. doi: 10.1093/nar/gkr007 en
dc.identifier.volume 39
dc.identifier.issued 10
dc.identifier.startpage 4220
dc.identifier.endpage 4234
dc.identifier.issn 0305-1048
dc.identifier.issn 1362-4962
dc.identifier.uri http://hdl.handle.net/10468/5024
dc.identifier.doi 10.1093/nar/gkr007
dc.description.abstract In eukaryotes, it is generally assumed that translation initiation occurs at the AUG codon closest to the messenger RNA 5' cap. However, in certain cases, initiation can occur at codons differing from AUG by a single nucleotide, especially the codons CUG, UUG, GUG, ACG, AUA and AUU. While non-AUG initiation has been experimentally verified for a handful of human genes, the full extent to which this phenomenon is utilized-both for increased coding capacity and potentially also for novel regulatory mechanisms-remains unclear. To address this issue, and hence to improve the quality of existing coding sequence annotations, we developed a methodology based on phylogenetic analysis of predicted 5' untranslated regions from orthologous genes. We use evolutionary signatures of protein-coding sequences as an indicator of translation initiation upstream of annotated coding sequences. Our search identified novel conserved potential non-AUG-initiated N-terminal extensions in 42 human genes including VANGL2, FGFR1, KCNN4, TRPV6, HDGF, CITED2, EIF4G3 and NTF3, and also affirmed the conservation of known non-AUG-initiated extensions in 17 other genes. In several instances, we have been able to obtain independent experimental evidence of the expression of non-AUG-initiated products from the previously published literature and ribosome profiling data. en
dc.description.sponsorship Wellcome Trust (088789); National Institute of Health (GM079523) 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/gkr007
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.uri http://creativecommons.org/licenses/by-nc/2.5
dc.subject Eukaryotic translation initiation en
dc.subject Hydroquinone NADH oxidase en
dc.subject Transfer RNA synthetases en
dc.subject Start codon recognition en
dc.subject Messenger RNAs en
dc.subject Saccharomyces-cerevisiae en
dc.subject Phylogenetic analysis en
dc.subject Maximum likelihood en
dc.subject Growth-factor en
dc.subject Gene encodes en
dc.title Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Pavel V. Baranov, Biochemistry & Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: P.Baranov@ucc.ie en
dc.internal.authorcontactother John F. Atkins, Biochemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: j.atkins@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 119278100
dc.contributor.funder National Institutes of Health
dc.contributor.funder Wellcome Trust
dc.contributor.funder Science Foundation Ireland
dc.description.status Peer reviewed en
dc.identifier.journaltitle Nucleic Acids Research en
dc.internal.IRISemailaddress p.baranov@ucc.ie en
dc.internal.IRISemailaddress j.atkins@ucc.ie
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/06/IN.1/B81/IE/RNA editing in humans: Identification prediction and therapeutic application/
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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© 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. Except where otherwise noted, this item's license is described as © 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.
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