Inhibition of RNase P RNA cleavage by aminoglycosides

A number of aminoglycosides have been reported to interact and interfere wi th the function of various RNA molecules, Among these are 16S rRNA, the gro up I intron, and the hammerhead ribozymes, In this report we show that clea vage 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 K-i value in th e micromolar range (35 mu M). 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 a minoglycosides compete with Mg2+ ions for functionally important divalent m etal ion binding sites. Thus, RNase P, which is an essential enzyme, is ind eed a potential drug target that can be used to develop new drugs by using various aminoglycosides as lead compounds.