title: Translation elongation factor 1A mutants with altered actin bundling activity show reduced aminoacyl-tRNA binding and alter initiation via eIF2α phosphorylation.
abstract: Apart from its canonical function in translation elongation, eukaryotic translation elongation factor 1A (eEF1A) has been shown to interact with the actin cytoskeleton. Amino acid substitutions in eEF1A that reduce its ability to bind and bundle actin in vitro cause improper actin organization in vivo and reduce total translation. Initial in vivo analysis indicated the reduced translation was through initiation. The mutant strains exhibit increased levels of phosphorylated initiation factor 2α (eIF2α) dependent on the presence of the general control non-derepressible 2 (Gcn2p) protein kinase. Gcn2p causes downregulation of total protein synthesis at initiation in response to increases in deacylated tRNA levels in the cell. Increased levels of eIF2α phosphorylation are not due to a general reduction in translation elongation as eEF2 and eEF3 mutants do not exhibit this effect. Deletion of GCN2 from the eEF1A actin bundling mutant strains revealed a second defect in translation. The eEF1A actin-bundling proteins exhibit changes in their elongation activity at the level of aminoacyl-tRNA binding in vitro. These findings implicate eEF1A in a feedback mechanism for regulating translation at initiation.
authors.forename: Winder B
authors.initials: WB
authors.lastname: Perez
authors.forename: Terri Goss
authors.initials: TG
authors.lastname: Kinzy
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010441:Peptide Chain Elongation, Translational / Q000502:physiology*; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D015852:Eukaryotic Initiation Factor-2; D020648:Peptide Elongation Factor 1; D012331:RNA, Fungal; D012346:RNA, Transfer, Amino Acyl; D029701:Saccharomyces cerevisiae Proteins; C512912:GCN2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases