Translational autoregulation of BZW1 and BZW2 expression by modulating the stringency of start codon selection

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dc.contributor.author Loughran, Gary
dc.contributor.author Firth, Andrew E.
dc.contributor.author Atkins, John F.
dc.contributor.author Ivanov, Ivaylo P.
dc.date.accessioned 2018-03-29T11:37:45Z
dc.date.available 2018-03-29T11:37:45Z
dc.date.issued 2018-02
dc.identifier.citation Loughran, G., Firth, A. E., Atkins, J. F. and Ivanov, I. P. (2018) 'Translational autoregulation of BZW1 and BZW2 expression by modulating the stringency of start codon selection', PLOS ONE, 13(2), e0192648 (13pp). doi:10.1371/journal.pone.0192648 en
dc.identifier.volume 13 en
dc.identifier.issued 2 en
dc.identifier.startpage e0192648-1 en
dc.identifier.endpage e0192648-13 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/5719
dc.identifier.doi 10.1371/journal.pone.0192648
dc.description.abstract The efficiency of start codon selection during ribosomal scanning in eukaryotic translation initiation is influenced by the context or flanking nucleotides surrounding the AUG codon. The levels of eukaryotic translation initiation factors 1 (eIF1) and 5 (eIF5) play critical roles in controlling the stringency of translation start site selection. The basic leucine zipper and W2 domain-containing proteins 1 and 2 (BZW1 and BZW2), also known as eIF5-mimic proteins, are paralogous human proteins containing C-terminal HEAT domains that resemble the HEAT domain of eIF5. We show that translation of mRNAs encoding BZW1 and BZW2 homologs in fungi, plants and metazoans is initiated by AUG codons in conserved unfavorable initiation contexts. This conservation is reminiscent of the conserved unfavorable initiation context that enables autoregulation of EIF1. We show that overexpression of BZW1 and BZW2 proteins enhances the stringency of start site selection, and that their poor initiation codons confer autoregulation on BZW1 and BZW2 mRNA translation. We also show that overexpression of these two proteins significantly diminishes the effect of overexpressing eIF5 on stringency of start codon selection, suggesting they antagonize this function of eIF5. These results reveal a surprising role for BZW1 and BZW2 in maintaining homeostatic stringency of start codon selection, and taking into account recent biochemical, genetic and structural insights into eukaryotic initiation, suggest a model for BZW1 and BZW2 function. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.rights This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. en
dc.rights.uri https://creativecommons.org/publicdomain/zero/1.0/ en
dc.subject Translation initiation en
dc.subject Hyperexpression techniques en
dc.subject Luciferase en
dc.subject Eukaryota en
dc.subject Algae en
dc.subject Protein translation en
dc.subject Messenger RNA en
dc.subject Sequence databases en
dc.title Translational autoregulation of BZW1 and BZW2 expression by modulating the stringency of start codon selection en
dc.type Article (peer-reviewed) 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.date.updated 2018-03-29T11:17:14Z
dc.description.version Published Version en
dc.internal.rssid 431799751
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Wellcome Trust en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Plos One en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.atkins@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IP/1492/IE/Using ribosome profiling to study translation initiation/elongation and facilitate optimization of protein synthesis/ en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/13/IA/1853/IE/Dynamic redefinition of codons: From antivirals to an essential micronutrient/ en


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This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Except where otherwise noted, this item's license is described as This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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