Initiation-shift of trans-translation by aminoglycosides.

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Konno T, Kurita D, Takahashi T, Muto A, Himeno H

Initiation-shift of trans-translation by aminoglycosides.

Nucleic Acids Symp Ser (Oxf). 2004;(48):299-300.

PubMed ID

17150597 [ View in PubMed

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Abstract

Trans-translation is an unusual translation in which tmRNA plays a dual function as a tRNA and an mRNA to relieve the stalled translation on the ribosome. In this study, we examined the effects of several kinds of aminoglycoside antibiotics, on trans-translation in vitro. A chemical footprinting study revealed that paromomycins bind tmRNA in the tRNA domain and in the middle of the long helix between tRNA and mRNA domains. Paromomycin bound in the tRNA domain inhibited aminoacylation, and the inhibition was suppressed by the addition of SmpB, a tmRNA binding protein. It was also found that paromomycin causes a shift of the translation-resuming point on tmRNA by -1. The effect on initiation-shift was suppressed by a mutation at the paromomycin binding site in 16S rRNA, but not by mutations in tmRNA. The effect of paromomycin on trans-translation differs substantially from that on canonical translation, in which it induces miscoding by modulating the A site of the decoding helix of the small subunit RNA of the ribosome. A minimal structure that causes initiation-shift was identified.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Paromomycin	16S ribosomal RNA	Nucleotide	Enteric bacteria and other eubacteria	Yes	Inhibitor	Details