Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences
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.contributor.funder | National Institutes of Health | |
dc.contributor.funder | Wellcome Trust | |
dc.contributor.funder | Science Foundation Ireland | |
dc.date.accessioned | 2017-11-14T13:24:31Z | |
dc.date.available | 2017-11-14T13:24:31Z | |
dc.date.issued | 2011 | |
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.description.status | Peer reviewed | en |
dc.description.version | Published Version | en |
dc.format.mimetype | application/pdf | en |
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.doi | 10.1093/nar/gkr007 | |
dc.identifier.endpage | 4234 | |
dc.identifier.issn | 0305-1048 | |
dc.identifier.issn | 1362-4962 | |
dc.identifier.issued | 10 | |
dc.identifier.journaltitle | Nucleic Acids Research | en |
dc.identifier.startpage | 4220 | |
dc.identifier.uri | https://hdl.handle.net/10468/5024 | |
dc.identifier.volume | 39 | |
dc.language.iso | en | en |
dc.publisher | Oxford University Press | en |
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/ | |
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 |
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