Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5

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dc.contributor.authorLoughran, Gary
dc.contributor.authorSachs, Matthew S.
dc.contributor.authorAtkins, John F.
dc.contributor.authorIvanov, Ivaylo P.
dc.contributor.funderNational Institutes of Health
dc.contributor.funderScience Foundation Ireland
dc.date.accessioned2017-11-14T13:24:30Z
dc.date.available2017-11-14T13:24:30Z
dc.date.issued2012
dc.description.abstractAn AUG in an optimal nucleotide context is the preferred translation initiation site in eukaryotic cells. Interactions among translation initiation factors, including eIF1 and eIF5, govern start codon selection. Experiments described here showed that high intracellular eIF5 levels reduced the stringency of start codon selection in human cells. In contrast, high intracellular eIF1 levels increased stringency. High levels of eIF5 induced translation of inhibitory upstream open reading frames (uORFs) in eIF5 mRNA that initiate with AUG codons in conserved poor contexts. This resulted in reduced translation from the downstream eIF5 start codon, indicating that eIF5 autoregulates its own synthesis. As with eIF1, which is also autoregulated through translation initiation, features contributing to eIF5 autoregulation show deep evolutionary conservation. The results obtained provide the basis for a model in which auto- and cross-regulation of eIF5 and eIF1 translation establish a regulatory feedback loop that would stabilize the stringency of start codon selection.en
dc.description.sponsorshipNational Institutes of Health (R01 GM079523; R01 GM47498)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLoughran, G., Sachs, M. S., Atkins, J. F. and Ivanov, I. P. (2012) 'Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5', Nucleic Acids Research, 40(7), pp. 2898-2906. doi: 10.1093/nar/gkr1192en
dc.identifier.doi10.1093/nar/gkr1192
dc.identifier.endpage2906
dc.identifier.issn0305-1048
dc.identifier.issued7
dc.identifier.journaltitleNucleic Acids Researchen
dc.identifier.startpage2898
dc.identifier.urihttps://hdl.handle.net/10468/5022
dc.identifier.volume40
dc.language.isoenen
dc.publisherOxford University Pressen
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/gkr1192
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/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc/3.0/
dc.subjectOpen reading framesen
dc.subject40S ribosomal-subuniten
dc.subjectMammalian cellsen
dc.subjectMessenger RNAsen
dc.subjectFactor IF3en
dc.subjectUpstreamen
dc.subjectProteinen
dc.subjectExpressionen
dc.subjectContexten
dc.subjectGeneen
dc.titleStringency of start codon selection modulates autoregulation of translation initiation factor eIF5en
dc.typeArticle (peer-reviewed)en
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