A FUNCTIONAL PEPTIDE ENCODED IN THE ESCHERICHIA-COLI 23S RIBOSOMAL-RNA

A pentapeptide open reading frame equipped with a canonical ribosome-b inding site is present in the Escherichia coli 23S rRNA. Overexpressio n of 23S rRNA fragments containing the mini-gene renders cells resista nt to the ribosome-inhibiting antibiotic erythromycin. Mutations that change either the initiator or stop codons of the peptide mini-gene re sult in the loss of erythromycin resistance. Nonsense mutations in the mini-gene also abolish erythromycin resistance, which can be restored in the presence of the suppressor tRNA, thus proving that expression of the rRNA-encoded peptide is essential for the resistance phenotype. The ribosome appears to be the likely target of action of the rRNA-en coded pentapeptide, because in vitro translation of the peptide mini-g ene decreases the inhibitory action of erythromycin on cell-free prote in synthesis. Thus, the new mechanism of drug resistance reveals that in addition to the structural and functional role of rRNA in the ribos ome, it may also have a peptide-coding function.