Iron-mediated degradation of ribosomes under oxidative stress is attenuated by manganese |
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Authors: | Daniel G. J. Smethurst Nikolay Kovalev Erica R. McKenzie Dimitri G. Pestov Natalia Shcherbik |
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Affiliation: | 1.Department of Cell Biology and Neuroscience, Rowan University, School of Osteopathic Medicine, Stratford, New Jersey, USA;2.Civil and Environmental Engineering Department, Temple University, Philadelphia, Pennsylvania, USA |
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Abstract: | 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 Mg2+ for structure. Recent work has indicated that other metal cations can substitute for Mg2+, 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 Fe2+ and the ribosome and identify Mn2+ as a factor capable of attenuating oxidant-induced Fe2+-mediated degradation of rRNA. We report that Fe2+ promotes degradation of all rRNA species of the yeast ribosome and that it is bound directly to RNA molecules. Furthermore, we demonstrate that Mn2+ competes with Fe2+ for rRNA-binding sites and that protection of ribosomes from Fe2+-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. |
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Keywords: | ribosomal ribonucleic acid (rRNA) RNA folding ribosome ribosome structure degradation of ribosomes oxidative stress oxidants iron iron metabolism metals manganese yeast cell viability |
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