title: Rps5-Rps16 communication is essential for efficient translation initiation in yeast S. cerevisiae.
abstract: Conserved ribosomal proteins frequently harbor additional segments in eukaryotes not found in bacteria, which could facilitate eukaryotic-specific reactions in the initiation phase of protein synthesis. Here we provide evidence showing that truncation of the N-terminal domain (NTD) of yeast Rps5 (absent in bacterial ortholog S7) impairs translation initiation, cell growth and induction of GCN4 mRNA translation in a manner suggesting incomplete assembly of 48S preinitiation complexes (PICs) at upstream AUG codons in GCN4 mRNA. Rps5 mutations evoke accumulation of factors on native 40S subunits normally released on conversion of 48S PICs to 80S initiation complexes (ICs) and this abnormality and related phenotypes are mitigated by the SUI5 variant of eIF5. Remarkably, similar effects are observed by substitution of Lys45 in the Rps5-NTD, involved in contact with Rps16, and by eliminating the last two residues of the C-terminal tail (CTT) of Rps16, believed to contact initiator tRNA base-paired to AUG in the P site. We propose that Rps5-NTD-Rps16-NTD interaction modulates Rps16-CTT association with Met-tRNAi (Met) to promote a functional 48S PIC.
authors.affiliation: Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Supriya
authors.initials: S
authors.lastname: Jindal
authors.affiliation: Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Amber A
authors.initials: AA
authors.lastname: Bentley
authors.affiliation: Laboratory of Gene Regulation and Development, Eunice K. Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Alan G
authors.initials: AG
authors.lastname: Hinnebusch
authors.affiliation: Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA a.komar@csuohio.edu.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Komar
mesh_terms: D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010442:Peptide Chain Initiation, Translational; D054730:Protein Interaction Domains and Motifs; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D039642:Eukaryotic Initiation Factors; C000592358:RPS16 protein, S cerevisiae; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C030831:ribosomal protein S5