The origins of RNA catalysis in ribozymes

The discovery of RNA catalysis provided a paradigm shift in biology, insight into the evolution of life on the planet and a challenge to understand its mechanistic origins. RNA has limited catalytic resources that must be used to maximal effect. Consequently, RNA catalysis tends to be multifactorial, with several processes contributing to an overall significant enhancement of reaction rate. These include general acid-base catalysis, electrostatic effects, and substrate orientation and proximity. The main players are the RNA nucleobases and bound metal ions. Although most ribozymes carry out phosphoryl transfer, the same considerations appear to apply to peptidyl transfer in the ribosome.