Topic: Transition metal ions as ribosome co-factors: functional interplay between magnesium, iron, and manganese

Abstract: The ribosome is a massive ribonucleoprotein complex that depends heavily on magnesium to maintain its structure. However, the early Earth environment, in which the ribosome was established, was chemically different, with greater levels of available iron and manganese and little free oxygen. It has been proposed that in an ancient ribosome, the folding of rRNAs was stabilized by ions of iron, which did not affect ribosome biogenesis. However, atmosphere oxygenation and Fenton reaction-induced (Fe2++ H2 O2 Fe3+ + •HO + OH-) iron toxicity, forced Fe2+ replacement by non-toxic Mg2+. This raises questions about alternative metal co-factors’ role in ribosome evolution and in the biogenesis/maintenance of modern ribosomes. To elucidate details of interactions between Fe2+ and ribosomes, we assessed the integrity of ribosomes from Saccharomyces cerevisiae following oxidative stress in vitro and in cells. We found that rRNAs coordinate Fe2+ directly at the selected sites without affecting ribosome translational competency. However, high Fe2+ promotes degradation of all rRNA species. Furthermore, we identified Mn2+ as another ribosome factor capable of attenuating Fe-mediated hydrolysis of rRNAs, suggesting Fe/Mn competition for rRNAs' binding sites. As Mn2+ is Fenton-inactive, it protects rRNAs from hydrolysis and restores cell viability, thus, controlling ribosome stability, especially under oxidative stress. Together, our data provide strong evidence that, through the course of evolution, a eukaryotic ribosome retained the capability to replace native Mg2+ with alternative divalent metal ions of a similar radius, which might play a regulatory role during gene expression as a means of adjustment to environmental changes.