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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.date.accessioned2011-08-29T10:32:05Z
dc.date.available2011-08-29T10:32:05Z
dc.date.issued2011-05
dc.identifier.citationIdentification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences. 2011, 39 (10):4220-34 Nucleic Acids Res.en
dc.identifier.issn1362-4962
dc.identifier.pmid21266472
dc.identifier.doi10.1093/nar/gkr007
dc.identifier.urihttp://hdl.handle.net/10147/141080
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.
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/21266472en
dc.subject.mesh5' Untranslated Regions
dc.subject.meshAlternative Splicing
dc.subject.meshBase Sequence
dc.subject.meshBlotting, Western
dc.subject.meshCodon, Initiator
dc.subject.meshConserved Sequence
dc.subject.meshEvolution, Molecular
dc.subject.meshHumans
dc.subject.meshPhylogeny
dc.subject.meshRNA, Messenger
dc.subject.meshSequence Alignment
dc.subject.meshSequence Analysis, RNA
dc.titleIdentification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences.en
dc.typeArticleen
dc.contributor.departmentBioSciences Institute, University College Cork, Cork, Ireland. iivanov@genetics.utah.eduen
dc.identifier.journalNucleic acids researchen
refterms.dateFOA2018-08-22T13:33:02Z
html.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.


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