Inhibition of RNase P RNA cleavage by aminoglycosides
- Proc Natl Acad Sci U S A. 1999 May 25;96(11):6155-60. doi: 10.1073/pnas.96.11.6155.
- 1. Department of Cell and Molecular Biology, Box 596, Biomedical Center, Uppsala University, SE-751 24 Uppsala, Sweden.
A number of aminoglycosides have been reported to interact and interfere with the function of various RNA molecules. Among these are 16S rRNA, the group I intron, and the hammerhead ribozymes. In this report we show that cleavage by RNase P RNA in the absence as well as in the presence of the RNase P protein is inhibited by several aminoglycosides. Among the ones we tested, neomycin B was found to be the strongest inhibitor with a Ki value in the micromolar range (35 microM). Studies of lead(II)-induced cleavage of RNase P RNA suggested that binding of neomycin B interfered with the binding of divalent metal ions to the RNA. Taken together, our findings suggest that aminoglycosides compete with Mg2+ ions for functionally important divalent metal ion binding sites. Thus, RNase P, which is an essential enzyme, is indeed a potential drug target that can be used to develop new drugs by using various aminoglycosides as lead compounds.