Modulation of RNA function by aminoglycoside antibiotics.

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Schroeder R, Waldsich C, Wank H

Modulation of RNA function by aminoglycoside antibiotics.

EMBO J. 2000 Jan 4;19(1):1-9.

PubMed ID

10619838 [ View in PubMed

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Abstract

One of the most important families of antibiotics are the aminoglycosides, including drugs such as neomycin B, paromomycin, gentamicin and streptomycin. With the discovery of the catalytic potential of RNA, these antibiotics became very popular due to their RNA-binding capacity. They serve for the analysis of RNA function as well as for the study of RNA as a potential therapeutic target. Improvements in RNA structure determination recently provided first insights into the decoding site of the ribosome at high resolution and how aminoglycosides might induce misreading of the genetic code. In addition to inhibiting prokaryotic translation, aminoglycosides inhibit several catalytic RNAs such as self-splicing group I introns, RNase P and small ribozymes in vitro. Furthermore, these antibiotics interfere with human immunodeficiency virus (HIV) replication by disrupting essential RNA-protein contacts. Most exciting is the potential of many RNA-binding antibiotics to stimulate RNA activities, conceiving small-molecule partners for the hypothesis of an ancient RNA world. SELEX (systematic evolution of ligands by exponential enrichment) has been used in this evolutionary game leading to small synthetic RNAs, whose NMR structures gave valuable information on how aminoglycosides interact with RNA, which could possibly be used in applied science.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Gentamicin	16S ribosomal RNA	Nucleotide	Enteric bacteria and other eubacteria	Yes	Binder	Details
Gentamicin	30S ribosomal protein S12	Protein	Escherichia coli (strain K12)	Yes	Binder	Details
Gentamicin C1a	16S ribosomal RNA	Nucleotide	Enteric bacteria and other eubacteria	Yes	Adduct	Details
Gentamicin C1a	30S ribosomal protein S12	Protein	Escherichia coli (strain K12)	Yes	Adduct	Details