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An alcohol dehydrogenase ribozyme


We report an RNA molecule that exhibits activity analogous to that of alcohol dehydrogenase (ADH). Directed in vitro evolution was used to enrich nicotinamide adenine dinucleotide (NAD+)–dependent redox-active RNAs from a combinatorial pool. The most active ribozyme in the population forms a compact pseudoknotted structure and oxidizes an alcohol seven orders of magnitude faster than the estimated spontaneous rate. Moreover, this ADH RNA was coupled with a redox relay between NADH and flavin adenine dinucleotide to give a NAD+-regeneration system. Our demonstration of the redox ability of RNA adds support to an RNA-based metabolic system in ancient life.

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Figure 1: In vitro selection of ADH ribozymes.
Figure 2: Product analyses of the benzaldehyde generated by ribox02.
Figure 3: The proposed secondary structure of 1-ribox02.
Figure 4: A multicomponent redox system involving 1-ribox02, NAD+/NADH and FAD/FADH2.


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This work was supported by a grant from the US National Science Foundation (H.S). S.T. acknowledges the JSPS Research Fellowships for Research Abroad. We thank all members of Suga and Bright groups, in particular D.R.W. Hodgson and H. Murakami for invaluable discussions and C.A. Munson for assistance with fluorescent measurements.

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Correspondence to Hiroaki Suga.

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Tsukiji, S., Pattnaik, S. & Suga, H. An alcohol dehydrogenase ribozyme. Nat Struct Mol Biol 10, 713–717 (2003).

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