Open AccessInhibition of RNase P RNA cleavage by aminoglycosides
Author(s) -
Nils Mikkelsen,
Mathias Brännvall,
Anders Virtanen,
Leif A. Kirsebom
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.11.6155
Subject(s) - ribozyme , rnase p , rna , neomycin , cleavage (geology) , rnase h , chemistry , binding site , biochemistry , divalent , ribonuclease iii , ribonuclease , biology , microbiology and biotechnology , antibiotics , gene , rna interference , paleontology , organic chemistry , fracture (geology)
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 aK i value in the micromolar range (35 μM). 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.