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.