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.
Bibliographical noteFunding Information:
J.W.S. is an investigator of the Howard Hughes Medical Institute. This work was supported in part by grants from the National Science Foundation [CHE-1607034] and the Simons Foundation  to J.W.S. The authors thank Dr. Ayan Pal and Dr. Anders Bjorkbom for glovebox installation and maintenance. The authors also thank Dr. Chun-Pong Tam, Dr. Claudia Bonfio, Dr. Neha P. Kamat, and Dr. David C. Catling for helpful discussions and comments on the manuscript.