TY - JOUR T1 - Ferrous iron folds rRNA and mediates translation JF - bioRxiv DO - 10.1101/256958 SP - 256958 AU - Marcus S. Bray AU - Tim K. Lenz AU - Jessica C. Bowman AU - Anton S. Petrov AU - Amit R. Reddi AU - Nicholas V. Hud AU - Loren Dean Williams AU - Jennifer B. Glass Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/03/05/256958.abstract N2 - The ubiquity of Fe2+ in life, despite its insolubility in the presence of oxygen, appears to stem from conditions of the ancient Earth. Today, Mg2+ is an essential cofactor with diverse structural and functional roles in life’s oldest macromolecular machine, the translation system. We tested whether anoxia and Fe2+ 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+ vs. Fe2+ on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe2+ could mediate protein production, and quantified ribosomal iron content. We found that: (i) Fe2+ and Mg2+ had strikingly similar effects on rRNA folding; (ii) Fe2+ can replace Mg2+ as the dominant divalent cation during translation of mRNA to functional protein; (iii) Fe2+ associated extensively with the ribosome. Given that the translation system originated and matured when Fe2+ was abundant, these findings suggest that Fe2+ played a role in early ribosomal evolution.SIGNIFICANCE Ribosomes are found in every living organisms where they are responsible for the translation of messenger RNA into protein. The ribosome’s centrality to cell function is underscored by its evolutionary conservation; the core structure has changed little since its inception ∼4 billion years ago when ecosystems were anoxic and Fe2+-rich. The ribosome is a model system for the study of bioinorganic chemistry, owing to the many highly coordinated divalent metal cations that are essential to its function. We studied the structure, function, and cation content of the ribosome under early Earth conditions, (high-Fe2+, low-O2). Our results expand the role of Fe2+ in ancient and extant biochemistry as a cofactor for ribosomal structure and function. ER -