Misreading of RNA Codewords Induced by Aminoglycoside Antibiotics

Abstract

The aminoglycoside antibiotics streptomycin, neomycin, kanamycin, paromomycin, gentamicin, hygromycin B, and viomycin all disturb the fidelity of the reading of polyribonucleotides in polypeptide synthesis. This effect is seen with all four homopolymers: poly U, poly C, poly A, and poly I. The extent and the spectrum of misreading vary with the antibiotic used and with the sRNA concentration. The antibiotics also influence the incorporation of the "correct" amino acid: with poly A they cause either stimulation or inhibition of lysine incorporation, depending on the sRNA concentration; poly C-directed proline incorporation was stimulated at all sRNA concentrations tested; and with poly U-directed phenylalanine incorporation the drugs were only inhibitory with most extracts. In all systems, with increasing sRNA the inhibition by the drug of "correct" reading became more prominent, and the relative misreading less prominent. In the light of recent knowledge of coding triplets, the effects observed suggest that aminoglycosides can (a) cause misreading of only one base at a time in UUU and CCC triplets, but of all three in AAA or III; (b) cause misreading of a base in only the 59 and the internal position in the pyrimidine codons, but in all three positions in the purine codons; and (c) allow both transition misreadings (purine to purine, or pyrimidine to pyrimidine) and transversion misreadings (purine to pyrimidine, or pyrimidine to purine). Transversion misreadings would seem to be rare in pyrimidine-containing polymers.