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

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dc.contributor.author Loughran, Gary
dc.contributor.author Sachs, Matthew S.
dc.contributor.author Atkins, John F.
dc.contributor.author Ivanov, Ivaylo P.
dc.date.accessioned 2017-11-14T13:24:30Z
dc.date.available 2017-11-14T13:24:30Z
dc.date.issued 2012
dc.identifier.citation Loughran, 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/gkr1192 en
dc.identifier.volume 40
dc.identifier.issued 7
dc.identifier.startpage 2898
dc.identifier.endpage 2906
dc.identifier.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/10468/5022
dc.identifier.doi 10.1093/nar/gkr1192
dc.description.abstract An 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.sponsorship National Institutes of Health (R01 GM079523; R01 GM47498) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Oxford University Press en
dc.relation.uri https://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.uri https://creativecommons.org/licenses/by-nc/3.0/
dc.subject Open reading frames en
dc.subject 40S ribosomal-subunit en
dc.subject Mammalian cells en
dc.subject Messenger RNAs en
dc.subject Factor IF3 en
dc.subject Upstream en
dc.subject Protein en
dc.subject Expression en
dc.subject Context en
dc.subject Gene en
dc.title Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5 en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Ivaylo Ivanov, Biochemistry and Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000. Email: i.ivanov@ucc.ie en
dc.internal.authorcontactother John F. Atkins, Biochemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: j.atkins@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 146554394
dc.contributor.funder National Institutes of Health
dc.contributor.funder Science Foundation Ireland
dc.description.status Peer reviewed en
dc.identifier.journaltitle Nucleic Acids Research en
dc.internal.IRISemailaddress i.ivanov@ucc.ie en
dc.internal.IRISemailaddress j.atkins@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/08/IN.1/B1889/IE/Altered Genetic Code Readout/


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© 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. Except where otherwise noted, this item's license is described as © 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.
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