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Article: eIF1 controls multiple steps in start codon recognition during eukaryotic translation initiation

TitleeIF1 controls multiple steps in start codon recognition during eukaryotic translation initiation
Authors
Issue Date2009
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmb
Citation
Journal of Molecular Biology, 2009, v. 394 n. 2, p. 268-285 How to Cite?
AbstractEukaryotic translation initiation factor (eIF) 1 is a central mediator of start codon recognition. Dissociation of eIF1 from the preinitiation complex (PIC) allows release of phosphate from the G-protein factor eIF2, triggering downstream events in initiation. Mutations that weaken binding of eIF1 to the PIC decrease the fidelity of start codon recognition (Sui(-) phenotype) by allowing increased eIF1 release at non-AUG codons. Consistent with this, overexpression of these mutant proteins suppresses their Sui(-) phenotypes. Here, we have examined mutations at the penultimate residue of eIF1, G107, that produce Sui(-) phenotypes without increasing the rate of eIF1 release. We provide evidence that, in addition to its role in gating phosphate release, dissociation of eIF1 triggers conversion from an open, scanning-competent state of the PIC to a stable, closed one. We also show that eIF5 antagonizes binding of eIF1 to the complex and that key interactions of eIF1 with its partners are modulated by the charge at and around G107. Our data indicate that eIF1 plays multiple roles in start codon recognition and suggest that prior to AUG recognition it prevents eIF5 from binding to a key site in the PIC required for triggering downstream events.
Persistent Identifierhttp://hdl.handle.net/10722/129526
ISSN
2015 Impact Factor: 4.517
2015 SCImago Journal Rankings: 3.002
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
NIHGM62128
NIH NICHD
Funding Information:

We thank members of our laboratories and Tom Dever for comments on the manuscript. This work was funded by a grant from the NIH to J.R.L. (GM62128) and by the Intramural Research Program of the NIH NICHD to A.G.H.

 

DC FieldValueLanguage
dc.contributor.authorNanda, JSen_US
dc.contributor.authorCheung, YNen_US
dc.contributor.authorTakacs, JEen_US
dc.contributor.authorMartin-Marcos, Pen_US
dc.contributor.authorSaini, AKen_US
dc.contributor.authorHinnebusch, AGen_US
dc.contributor.authorLorsch, JRen_US
dc.date.accessioned2010-12-23T08:38:26Z-
dc.date.available2010-12-23T08:38:26Z-
dc.date.issued2009en_US
dc.identifier.citationJournal of Molecular Biology, 2009, v. 394 n. 2, p. 268-285en_US
dc.identifier.issn0022-2836-
dc.identifier.urihttp://hdl.handle.net/10722/129526-
dc.description.abstractEukaryotic translation initiation factor (eIF) 1 is a central mediator of start codon recognition. Dissociation of eIF1 from the preinitiation complex (PIC) allows release of phosphate from the G-protein factor eIF2, triggering downstream events in initiation. Mutations that weaken binding of eIF1 to the PIC decrease the fidelity of start codon recognition (Sui(-) phenotype) by allowing increased eIF1 release at non-AUG codons. Consistent with this, overexpression of these mutant proteins suppresses their Sui(-) phenotypes. Here, we have examined mutations at the penultimate residue of eIF1, G107, that produce Sui(-) phenotypes without increasing the rate of eIF1 release. We provide evidence that, in addition to its role in gating phosphate release, dissociation of eIF1 triggers conversion from an open, scanning-competent state of the PIC to a stable, closed one. We also show that eIF5 antagonizes binding of eIF1 to the complex and that key interactions of eIF1 with its partners are modulated by the charge at and around G107. Our data indicate that eIF1 plays multiple roles in start codon recognition and suggest that prior to AUG recognition it prevents eIF5 from binding to a key site in the PIC required for triggering downstream events.-
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmb-
dc.relation.ispartofJournal of Molecular Biologyen_US
dc.rightsAppropriate Bibliographic Citation:Authors posting Accepted Author Manuscript online should later add a citation for the Published Journal Article indicating that the Article was subsequently published, and may mention the journal title provided that they add the following text at the beginning of the document: “NOTICE: this is the author’s version of a work that was accepted for publication in <Journal title>. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in PUBLICATION, [VOL#, ISSUE#, (DATE)] DOI#”-
dc.subject.meshAmino Acid Substitution-
dc.subject.meshAnimals-
dc.subject.meshCodon, Initiator - genetics - metabolism-
dc.subject.meshEukaryotic Initiation Factor-1 - genetics - metabolism-
dc.subject.meshPeptide Chain Initiation, Translational-
dc.titleeIF1 controls multiple steps in start codon recognition during eukaryotic translation initiationen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-2836&volume=394&issue=2&spage=268&epage=285&date=2009&atitle=eIF1+controls+multiple+steps+in+start+codon+recognition+during+eukaryotic+translation+initiation-
dc.identifier.emailCheung, YN: jennyync@yahoo.comen_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.jmb.2009.09.017-
dc.identifier.pmid19751744-
dc.identifier.pmcidPMC2783965-
dc.identifier.scopuseid_2-s2.0-70350557033-
dc.identifier.hkuros176719en_US
dc.identifier.volume394en_US
dc.identifier.issue2-
dc.identifier.spage268en_US
dc.identifier.epage285-
dc.identifier.isiWOS:000271985700009-
dc.identifier.citeulike5793823-

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