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Gerbasi, VR, Weaver, CM, Hill, S, Friedman, DB and Link, AJ (2004) Yeast Asc1p and mammalian RACK1 are functionally orthologous core 40S ribosomal proteins that repress gene expression. Mol. Cell. Biol. 24:8276-87
Translation of mRNA into protein is a fundamental step in eukaryotic gene expression requiring the large (60S) and small (40S) ribosome subunits and associated proteins. By modern proteomic approaches, we previously identified a novel 40S-associated protein named Asc1p in budding yeast and RACK1 in mammals. The goals of this study were to establish Asc1p or RACK1 as a core conserved eukaryotic ribosomal protein and to determine the role of Asc1p or RACK1 in translational control. We provide biochemical, evolutionary, genetic, and functional evidence showing that Asc1p or RACK1 is indeed a conserved core component of the eukaryotic ribosome. We also show that purified Asc1p-deficient ribosomes have increased translational activity compared to that of wild-type yeast ribosomes. Further, we demonstrate that asc1Delta null strains have increased levels of specific proteins in vivo and that this molecular phenotype is complemented by either Asc1p or RACK1. Our data suggest that one of Asc1p's or RACK1's functions is to repress gene expression.
Adaptor Proteins, Signal Transducing; Animals; Base Sequence; Cell Line; DNA, Complementary/genetics; DNA, Fungal/genetics; Evolution, Molecular; GTP-Binding Proteins; Gene Deletion; Genes, Fungal; Genetic Complementation Test; Humans; Mice; Phenotype; Protein Biosynthesis; Receptors, Cell Surface/chemistry; Receptors, Cell Surface/genetics; Receptors, Cell Surface/metabolism; Repressor Proteins/chemistry; Repressor Proteins/genetics; Repressor Proteins/metabolism; Ribosomal Proteins/chemistry; Ribosomal Proteins/genetics; Ribosomal Proteins/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Species Specificity