The yeast omnipotent suppressor SUP46 encodes a ribosomal protein which is a functional and structural homolog of the Escherichia coli S4 ram protein.

Abstract

The accurate synthesis of proteins is crucial to the existence of a cell. In yeast, several genes that affect the fidelity of translation have been identified (e.g., omnipotent suppressors, antisuppressors and allosuppressors). We have found that the dominant omnipotent suppressor SUP46 encodes the yeast ribosomal protein S13. S13 is encoded by two similar genes, but only the sup46 copy of the gene is able to fully complement the recessive phenotypes of SUP46 mutations. Both copies of the S13 genes contain introns. Unlike the introns of other duplicated ribosomal protein genes which are highly diverged, the duplicated S13 genes have two nearly identical DNA sequences of 25 and 31 bp in length within their introns. The SUP46 protein has significant homology to the S4 ribosomal protein in prokaryotic-type ribosomes. S4 is encoded by one of the ram (ribosomal ambiguity) genes in Escherichia coli which are the functional equivalent of omnipotent suppressors in yeast. Thus, SUP46 and S4 demonstrate functional as well as sequence conservation between prokaryotic and eukaryotic ribosomal proteins. SUP46 and S4 are most similar in their central amino acid sequences. Interestingly, the alterations resulting from the SUP46 mutations and the segment of the S4 protein involved in binding to the 16S rRNA are within this most conserved region.

Error-prone protein synthesis recapitulates early symptoms of Alzheimer disease in aging mice

“…To separate the role of a specific misfolded rogue protein from the principle question of mistranslation-induced random protein misfolding and its effect on neuronal health, we used a genetic model with genome-wide expression of error-prone translation, building upon Rps9 D94N, a well-known ribosomal ambiguity mutation (ram) in the lower eukaryote Saccharomyces cerevisiae (Masurekar et al, 1981;Vincent and Liebman, 1992). Ram mutations increase the natural error rate of translation and affect the initial phase of tRNA selection by reducing discrimination against near-cognate aatRNAs (Gromadski and Rodnina, 2004;Ogle and Ramakrishnan, 2005;Zaher and Green, 2010).…”

Modulation of efficiency of translation termination inSaccharomyces cerevisiae

“…Two dominant omnipotent SNMs, SUP44 and SUP46, were found to be mutant alleles of the genes RPS2 and RPS9 encoding the homologs of bacterial "ribosomal ambiguity" proteins, ram's, S4 and S5, respectively. [31][32][33][34] Also, an array of mutations modulating efficiency of translation termination was isolated in the gene for the Rps28 protein, a homolog of another bacterial ram protein, S12. Interestingly, Rps28 can alter translational accuracy in both directions: some of RPS28 mutations were SNMs, and some had an antisuppressor effect toward other nonsense suppressors, including SUP44 and SUP46.…”

NAM9 Nuclear Suppressor of Mitochondrial Ochre Mutations in Saccharomyces cerevisiae Codes for a Protein Homologous to S4 Ribosomal Proteins from Chloroplasts, Bacteria, and Eucaryotes

“…(note that the former is systematically more similar to the chloroplast proteins than the latter). The third subset comprises the cytoplasmic ribosomal S13 protein from S. cerevisiae, the gene for which has been isolated as an omnipotent --I suppressor SUP46 (63), the r-protein rp1O24 from Dictyostelium discoideum (58), and a putative protein coded by an ORF interspersing the region encoding fructose biphosphate aldolase in Trypanosoma brucei (62). The three latter proteins are practically as similar to each other as are the chloroplast or procaryote S4 proteins, and there is no doubt that they are homologous.…”