title: A functional peptide encoded in the Escherichia coli 23S rRNA.
abstract: A pentapeptide open reading frame equipped with a canonical ribosome-binding site is present in the Escherichia coli 23S rRNA. Overexpression of 23S rRNA fragments containing the mini-gene renders cells resistant to the ribosome-inhibiting antibiotic erythromycin. Mutations that change either the initiator or stop codons of the peptide mini-gene result 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-encoded pentapeptide, because in vitro translation of the peptide mini-gene decreases the inhibitory action of erythromycin on cell-free protein synthesis. Thus, the new mechanism of drug resistance reveals that in addition to the structural and functional role of rRNA in the ribosome, it may also have a peptide-coding function.
authors.affiliation: Center for Pharmaceutical Biotechnology, University of Illinois, Chicago 60607-7173, USA.
authors.forename: T
authors.initials: T
authors.lastname: Tenson
authors.forename: A
authors.initials: A
authors.lastname: DeBlasio
authors.forename: A
authors.initials: A
authors.lastname: Mankin
mesh_terms: D000595:Amino Acid Sequence; D000668:Ampicillin Resistance; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D004275:DNA, Ribosomal / Q000737:chemistry / Q000378:metabolism; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016153:Genes, Suppressor; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012338:RNA, Ribosomal, 23S / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D004275:DNA, Ribosomal; D012338:RNA, Ribosomal, 23S; D004917:Erythromycin