Catalysis of Template-Directed Nonenzymatic RNA Copying by Iron(II)

The study of nonenzymatic template-directed RNA copying is the experimental basis for the search for chemistry and reaction conditions consistent with prebiotic RNA replication. The most effective model systems for RNA copying have to date required a high concentration of Mg²⁺. Recently, Fe²⁺, which was abundant on the prebiotic anoxic Earth, was shown to promote the folding of RNA in a manner similar to the case of Mg²⁺, as a result of the two cations having similar interactions with phosphate groups. These observations raise the question of whether Fe²⁺ could have promoted RNA copying on the prebiotic Earth. Here, we demonstrate that Fe²⁺ is a better catalyst and promotes faster nonenzymatic RNA primer extension and ligation than Mg²⁺ when using 2-methylimidazole activated nucleotides in slightly acidic to neutral pH solutions. Thus, it appears likely that Fe²⁺ could have facilitated RNA replication and evolution in concert with other metal cations on the prebiotic Earth.