Multiple prebiotic metals mediate translation

Abstract

Today, Mg2+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 O2, high Fe2+, and high Mn2+) 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 Mg2+, Fe2+, and Mn2+on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe2+or Mn2+could mediate protein production, and quantified ribosomal metal content. We found that (i) Mg2+, Fe2+, and Mn2+had strikingly similar effects on rRNA folding; (ii) Fe2+and Mn2+can replace Mg2+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 Fe2+and Mn2+were abundant, these findings suggest that Fe2+and Mn2+played a role in early ribosomal evolution.