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

Abstract

Pb(II) is extremely efficient at depolymerizing RNA and studies on tRNAs have shown that site-specific cleavages in these molecules can be brought about by the action of Pb(II). We have observed, by difference Fourier analysis, 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.