Figure 1. Chemistry of pre-mRNA splicing and U2/U6 model showing sites sensitive to sulfur substitutions and rescued by thiophilic metal.

a, Reaction scheme (top) and transition state diagrams (bottom) for the two steps of nuclear pre-mRNA splicing. b–c, Models of the U2/U6 structure from the spliceosome (b) and domain V of a group II intron (c). Nucleotides where sulfur substitutions were shown previously to interfere with splicing^12–16 are coloured red; underlined U6 nucleotides were tested in this study; * indicates those positions where only the pro-S_p oxygen was substituted with sulfur; and boxed nucleotides provide ligands for metals at the catalytic stage (Fig. 2, ref. ²⁶).