Multiple prebiotic metals mediate translation

Today, Mg 2+ is an essential cofactor with diverse structural and functional roles in life’s oldest macromolecular machine, the translation system. We tested whether ancient Earth conditions (low O 2 , high Fe 2+ , and high Mn 2+ ) can revert the ribosome to a functional ancestral state. First, SHAPE (selective 2′-hydroxyl acylation analyzed by primer extension) was used to compare the effect of Mg 2+ , Fe 2+ , and Mn 2+ on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe 2+ or Mn 2+ could mediate protein production, and quantified ribosomal metal content. We found that ( i ) Mg 2+ , Fe 2+ , and Mn 2+ had strikingly similar effects on rRNA folding; ( ii ) Fe 2+ and Mn 2+ can replace Mg 2+ as the dominant divalent cation during translation of mRNA to functional protein; and ( iii ) Fe and Mn associate extensively with the ribosome. Given that the translation system originated and matured when Fe 2+ and Mn 2+ were abundant, these findings suggest that Fe 2+ and Mn 2+ played a role in early ribosomal evolution.