MUTATIONS IN EUKARYOTIC 18S RIBOSOMAL-RNA AFFECT TRANSLATIONAL FIDELITY AND RESISTANCE TO AMINOGLYCOSIDE ANTIBIOTICS

Mutations have been created in the Saccharomyces cerevisiae 18S rRNA g ene that correspond to those known to be involved in the control of tr anslational fidelity or antibiotic resistance in prokaryotes. Yeast st rains, in which essentially all chromosomal rDNA repeats are deleted a nd all cellular rRNAs are encoded by plasmid, have been constructed th at contain only mutant 18S rRNA. In Escherichia coli, a C-->U substitu tion at position 912 of the small subunit rRNA causes streptomycin res istance. Eukaryotes normally carry U at the corresponding position and are naturally resistant to streptomycin. We show that a U-C transitio n (rdn-4) at this position of the yeast 18S rRNA gene decreases resist ance to streptomycin. The rdn-4 mutation also increases resistance to paromomycin and G-418, and inhibits nonsense suppression induced by pa romomycin. The same phenotypes, as well as a slow growth phenotype, ar e also associated with rdn-2, whose prokaryotic counterpart, 517 G-->A , manifests itself as a suppressor rather than an antisuppressor. Neit her rdn-2- nor rdn-4-related phenotypes could be detected in the prese nce of the normal level of wild-type rDNA repeats. Our data demonstrat e that eukaryotic rRNA is involved in the control of translational fid elity, and indicate that rRNA features important for interactions with aminoglycosides have been conserved throughout evolution.