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RNA with iron(II) as a cofactor catalyses electron transfer

Nature Chemistry volume 5, pages 525–528 (2013)Cite this article

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Abstract

Mg2+ is essential for RNA folding and catalysis. However, for the first 1.5 billion years of life on Earth RNA inhabited an anoxic Earth with abundant and benign Fe2+. We hypothesize that Fe2+ was an RNA cofactor when iron was abundant, and was substantially replaced by Mg2+ during a period known as the ‘great oxidation’, brought on by photosynthesis. Here, we demonstrate that reversing this putative metal substitution in an anoxic environment, by removing Mg2+ and replacing it with Fe2+, expands the catalytic repertoire of RNA. Fe2+ can confer on some RNAs a previously uncharacterized ability to catalyse single-electron transfer. We propose that RNA function, in analogy with protein function, can be understood fully only in the context of association with a range of possible metals. The catalysis of electron transfer, requisite for metabolic activity, may have been attenuated in RNA by photosynthesis and the rise of O2.

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Figure 1: Some RNAs in combination with Fe2+ catalyse single-electron transfer.
Figure 2: Fe2+–RNA catalysed single-electron transfer reactions follow enzyme kinetics.

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Acknowledgements

The authors thank J. Bada, R. Hazen, K. Barefield, J. Sadighi and D. Jenson for helpful discussions. This work was supported by the National Aeronautics and Space Administration Astrobiology Institute (NNA09DA78A).

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Authors and Affiliations

  1. School of Chemistry and Biochemistry, School of Biology, and NASA Astrobiology Institute Center for Ribosomal Origins and Evolution, Georgia Institute of Technology, Atlanta, 30332, Georgia, USA

    Chiaolong Hsiao, I-Chun Chou, C. Denise Okafor, Jessica C. Bowman, Eric B. O'Neill, Shreyas S. Athavale, Anton S. Petrov, Nicholas V. Hud, Roger M. Wartell, Stephen C. Harvey & Loren Dean Williams

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  1. Chiaolong Hsiao
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Contributions

C.H., N.V.H, R.M.W., S.C.H. and L.D.W. conceived and designed the experiments and co-wrote the manuscript. C.H., C.D.O. and I-C.C. performed the experiments and analysed the data. J.C.B., E.B.O'N, S.S.A. and A.P. contributed materials and analysis tools. All the authors discussed the results and contributed to writing and editing the manuscript.

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Correspondence to Loren Dean Williams.

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The authors declare no competing financial interests.

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Hsiao, C., Chou, IC., Okafor, C. et al. RNA with iron(II) as a cofactor catalyses electron transfer. Nature Chem 5, 525–528 (2013). https://doi.org/10.1038/nchem.1649

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