Folding and Catalysis Near Life’s Origin: Support for Fe 2+ as a Dominant Divalent Cation

There is broad consensus that during and immediately following the origin of life, RNA was the single biopolymer or was among a small group of cooperating biopolymers. During the origin of life, the Archean Earth was anoxic; Fe2+ was abundant and relatively benign. We hypothesize that RNA used Fe2+ as a cofactor instead of, or along with, Mg2+ during the inception and early phases of biology, until the Great Oxidation Event (GOE). In this model, RNA participated in a metal substitution during the GOE, whereby Mg2+ replaced Fe2+ as the dominant RNA cofactor. A GOE-induced Fe2+ to Mg2+ substitution predicts that under ‘early Earth’ (anoxic) conditions, Fe2+ can participate in a variety of functions, including mediation of RNA folding and catalysis by ribozymes and proteins. Understanding the influence of Fe2+ on nucleic acid structure and function could provide an important link between the geological record and the ancestral biological world. This review focuses on experimental work investigating the interactions and functions of RNA and nucleic acid processing proteins with Fe2+ under anoxic, early Earth conditions.