dc.contributor.author	Loughran, Gary
dc.contributor.author	Firth, Andrew E.
dc.contributor.author	Atkins, John F.
dc.contributor.author	Ivanov, Ivaylo P.
dc.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	Wellcome Trust	en
dc.date.accessioned	2018-03-29T11:37:45Z
dc.date.available	2018-03-29T11:37:45Z
dc.date.issued	2018-02
dc.date.updated	2018-03-29T11:17:14Z
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.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
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.doi	10.1371/journal.pone.0192648
dc.identifier.endpage	e0192648-13	en
dc.identifier.issn	1932-6203
dc.identifier.issued	2	en
dc.identifier.journaltitle	Plos One	en
dc.identifier.startpage	e0192648-1	en
dc.identifier.uri	https://hdl.handle.net/10468/5719
dc.identifier.volume	13	en
dc.language.iso	en	en
dc.publisher	Public Library of Science	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
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

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

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