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

Hdl Handle:
http://hdl.handle.net/10147/141080
Title:
Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences.
Authors:
Ivanov, Ivaylo P; Firth, Andrew E; Michel, Audrey M; Atkins, John F; Baranov, Pavel V
Affiliation:
BioSciences Institute, University College Cork, Cork, Ireland. iivanov@genetics.utah.edu
Citation:
Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences. 2011, 39 (10):4220-34 Nucleic Acids Res.
Journal:
Nucleic acids research
Issue Date:
May-2011
URI:
http://hdl.handle.net/10147/141080
DOI:
10.1093/nar/gkr007
PubMed ID:
21266472
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/21266472
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.
Item Type:
Article
Language:
en
MeSH:
5' Untranslated Regions; Alternative Splicing; Base Sequence; Blotting, Western; Codon, Initiator; Conserved Sequence; Evolution, Molecular; Humans; Phylogeny; RNA, Messenger; Sequence Alignment; Sequence Analysis, RNA
ISSN:
1362-4962

Full metadata record

DC FieldValue Language
dc.contributor.authorIvanov, Ivaylo Pen
dc.contributor.authorFirth, Andrew Een
dc.contributor.authorMichel, Audrey Men
dc.contributor.authorAtkins, John Fen
dc.contributor.authorBaranov, Pavel Ven
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

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