Iron-mediated degradation of ribosomes under oxidative stress is attenuated by manganese.

Protein biosynthesis is fundamental to cellular life and requires the efficient functioning of the translational machinery. At the center of this machinery is the ribosome, a ribonucleoprotein complex that depends heavily on Mg(2+) for structure. Recent work has indicated that other metal cations can substitute for Mg(2+), raising questions about the role different metals may play in the maintenance of the ribosome under oxidative stress conditions. Here, we assess ribosomal integrity following oxidative stress both in vitro and in cells to elucidate details of the interactions between Fe(2+) and the ribosome and identify Mn(2+) as a factor capable of attenuating oxidant-induced Fe(2+)-mediated degradation of rRNA. We report that Fe(2+) promotes degradation of all rRNA species of the yeast ribosome and that it is bound directly to RNA molecules. Furthermore, we demonstrate that Mn(2+) competes with Fe(2+) for rRNA-binding sites and that protection of ribosomes from Fe(2+)-mediated rRNA hydrolysis correlates with the restoration of cell viability. Our data, therefore, suggest a relationship between these two transition metals in controlling ribosome stability under oxidative stress.