ANTIBIOTIC-INDUCED OLIGOMERIZATION OF GROUP-I INTRON RNA

Antibiotics act as inhibitors of various biological processes. Here we demonstrate that some tuberactinomycins, hitherto known as inhibitors of prokaryotic protein synthesis and of group I intron self-splicing, have a modulatory effect on group I intron RNAs. The linear intron, w hich is excised during the self-splicing process, is still an active m olecule capable of performing an intramolecular transesterification re sulting in a circular molecule. However, in the presence of sub-inhibi tory concentrations of tuberactinomycins, the intron reacts intermolec ularly leading to the formation of linear head-to-tail intron-oligomer s. The antibiotic stimulates the intron to react in tuans instead of i n cis. The phage T4-derived td intron uses the same sites for oligomer isation as for circularisation. Gel-retardation experiments demonstrat e that the intron RNA forms non-covalent complexes in the presence of the antibiotic. It might be envisaged that the role of these peptide a ntibiotics is to bridge RNA molecules mediating RNA-RNA interactions a nd thus enabling their reaction. The tuberactinomycins are further abl e to induce the interaction of heterologous introns. The ligation of t he T4 phage-derived td intron with the Tetrahymena rRNA intron is very efficient, resulting in molecules composed of two introns derived fro m different species. The td intron attacks the Tetraymena intron at va rious sites, which are located within double-stranded regions. These o bservations suggest that small molecules like these basic peptide anti biotics could have mediated RNA-RNA interactions in a pre-protein era. (C) 1996 Academic Press Limited