Isomerization of RNA Phosphodiester Linkages

Abstract

RNA phosphodiester linkages undergo two transesterification reactions catalyzed by Brönsted acids or bases, viz., cyclization to a 2′,3′-cyclic phosphate with concomitant release of the 5′-linked nucleoside and isomerization to a 2′,5′-linkage. While these processes are approximately as fast under acidic conditions, the cyclization gradually takes over on going to alkaline solutions. At physiological pH, the isomerization still successfully competes with the chain cleavage. Nevertheless, protein enzymes, ribozymes, and metal ion complexes with some exceptions catalyze only the cleavage reaction. The mechanistic reasons for the dissimilar pH dependence and susceptibility to catalysis are discussed.