RNA with iron(II) as a cofactor catalyses electron transfer

Mg²⁺ is essential for RNA folding and catalysis. However, for the first 1.5 billion years of life on Earth RNA inhabited an anoxic Earth with abundant and benign Fe²⁺. We hypothesize that Fe²⁺ was an RNA cofactor when iron was abundant, and was substantially replaced by Mg ²⁺ during a period known as the 'great oxidation', brought on by photosynthesis. Here, we demonstrate that reversing this putative metal substitution in an anoxic environment, by removing Mg²⁺ and replacing it with Fe²⁺, expands the catalytic repertoire of RNA. Fe ²⁺ can confer on some RNAs a previously uncharacterized ability to catalyse single-electron transfer. We propose that RNA function, in analogy with protein function, can be understood fully only in the context of association with a range of possible metals. The catalysis of electron transfer, requisite for metabolic activity, may have been attenuated in RNA by photosynthesis and the rise of O₂.