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

dc.contributor.authorIvanov, Ivaylo P.
dc.contributor.authorFirth, Andrew E.
dc.contributor.authorMichel, Audrey M.
dc.contributor.authorAtkins, John F.
dc.contributor.authorBaranov, Pavel V.
dc.contributor.funderNational Institutes of Health
dc.contributor.funderWellcome Trust
dc.contributor.funderScience Foundation Ireland
dc.date.accessioned2017-11-14T13:24:31Z
dc.date.available2017-11-14T13:24:31Z
dc.date.issued2011
dc.description.abstractIn 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.sponsorshipWellcome Trust (088789); National Institute of Health (GM079523)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationIvanov, 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/gkr007en
dc.identifier.doi10.1093/nar/gkr007
dc.identifier.endpage4234
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.issued10
dc.identifier.journaltitleNucleic Acids Researchen
dc.identifier.startpage4220
dc.identifier.urihttps://hdl.handle.net/10468/5024
dc.identifier.volume39
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.projectinfo: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.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/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.urihttp://creativecommons.org/licenses/by-nc/2.5
dc.subjectEukaryotic translation initiationen
dc.subjectHydroquinone NADH oxidaseen
dc.subjectTransfer RNA synthetasesen
dc.subjectStart codon recognitionen
dc.subjectMessenger RNAsen
dc.subjectSaccharomyces-cerevisiaeen
dc.subjectPhylogenetic analysisen
dc.subjectMaximum likelihooden
dc.subjectGrowth-factoren
dc.subjectGene encodesen
dc.titleIdentification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequencesen
dc.typeArticle (peer-reviewed)en
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