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Pb(II)-catalysed cleavage of the sugar–phosphate backbone of yeast tRNAPhe—implications for lead toxicity and self-splicing RNA


Pb(II) is extremely efficient at depolymerizing RNA1–5 and studies on tRNAs have shown that site-specific cleavages in these molecules can be brought about by the action of Pb(II)6. We have observed, by difference Fourier analysis7,8, sugar–phosphate strand scission between residues 17 and 18 in crystals of yeast tRNAPhe soaked in dilute Pb(II) solution at pH 7.4. We have also deduced the structure of the Pb(II)–tRNAPhe derivative at pH 5.0 where this cleavage reaction is considerably slower and report that, in this structure, the sugar–phosphate backbone remains intact. We have, therefore, a picture of the reactants (at pH 5.0) and products (at pH 7.4) of this cleavage reaction. From this crystallographic study, and associated biochemical work, we have formulated a possible mechanism for the cleavage reaction and also present here some general ideas on the action of metal ions on nucleic acids.

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Brown, R., Hingerty, B., Dewan, J. et al. Pb(II)-catalysed cleavage of the sugar–phosphate backbone of yeast tRNAPhe—implications for lead toxicity and self-splicing RNA. Nature 303, 543–546 (1983).

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