title: ABC50 mutants modify translation start codon selection.
abstract: ATP-binding cassette 50 (ABC50; also known as ABCF1) binds to eukaryotic initiation factor 2 (eIF2) and is required for efficient translation initiation. An essential step of this process is accurate recognition and selection of the initiation codon. It is widely accepted that the presence and movement of eIF1, eIF1A and eIF5 are key factors in modulating the stringency of start-site selection, which normally requires an AUG codon in an appropriate sequence context. In the present study, we show that expression of ABC50 mutants, which cannot hydrolyse ATP, decreases general translation and relaxes the discrimination against the use of non-AUG codons at translation start sites. These mutants do not appear to alter the association of key initiation factors to 40S subunits. The stringency of start-site selection can be restored through overexpression of eIF1, consistent with the role of that factor in enhancing stringency. The present study indicates that interfering with the function of ABC50 influences the accuracy of initiation codon selection.
authors.affiliation: *Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Stewart
authors.affiliation: *Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Cowan
authors.affiliation: *Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Perry
authors.affiliation: *Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Coldwell
authors.affiliation: *Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Proud
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D018387:Codon, Initiator / Q000235:genetics / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D006868:Hydrolysis; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D054682:Ribosome Subunits, Small, Eukaryotic / Q000235:genetics / Q000378:metabolism*
chemical_list: C115776:ABCF1 protein, human; D018528:ATP-Binding Cassette Transporters; D018387:Codon, Initiator; C410108:EIF1 protein, human; D039642:Eukaryotic Initiation Factors; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000255:Adenosine Triphosphate