Hammerhead Ribozymes: True Metal or Nucleobase Catalysis? Where Is the Catalytic Power from?

The hammerhead ribozyme was first considered as a metalloenzyme despite persistent inconsistencies between structural and functional data. In the last decade, metal ions were confirmed as catalysts in self-splicing ribozymes but displaced by nucleobases in self-cleaving ribozymes. However, a model of catalysis just relying on nucleobases as catalysts does not fully fit some recent data. Gathering and comparing data on metal ions in self-cleaving and self-splicing ribozymes, the roles of divalent metal ions and nucleobases are revisited. Hypothetical models based on cooperation between metal ions and nucleobases are proposed for the catalysis and evolution of this prototype in RNA catalysis.