Inhibition of RNA Phosphodiester Backbone Cleavage in the Presence of Organic Cations of Different Sizes

Abstract

Living cells contain various types of organic cations that may interact with nucleic acids. In order to understand the nucleic acid–binding properties of organic cations of different sizes, we investigated the ability of simple organic cations to inhibit the RNA phosphodiester bond cleavage promoted by Mg2+, Pb2+, and RNA‐cleaving serum proteins. Kinetic analysis using chimeric DNA–RNA oligonucleotides showed that the cleavage at ribonucleotide sites was inhibited in the presence of monovalent cations comprising alkyl chains or benzene rings. The comparison of the cleavage rates in the presence of quaternary ammonium and phosphonium ions indicated that the steric hindrance effect of organic cations on their binding to the RNA backbone is significant when the cation size is larger than the phosphate–phosphate distance of a single‐stranded nucleic acid. The cleavage inhibition was also observed for ribonucleotides located in long loops but not in short loops of oligonucleotide structures, indicating less efficient binding of bulky cations to structurally constrained regions. These results reveal the unique nucleic acid–binding properties of bulky cations distinct from those of metal ions.