Porphyrin metalation catalyzed by a small RNA molecule

We report here the isolation and characterization of a 35-nucleotide (nt) RNA that catalyzes the related Cu(II) insertion into mesoporphyrin IX with a kcat/Km value of 2100 M-1 s-1, close to the value for the metalation of mesoporphyrin with Fe(II) catalyzed by recombinant human ferrochelatase. This work demonstrates the ability of RNA to catalyze a reaction closely to that required for the biosynthesis of the essential cofactor, heme. The small size of the catalytic sequence motif found here should facilitate structural studies. Moreover, mutants of this RNA may be selected to display other porphyrin-based activities: ferrochelatase activity, reversible oxygen binding with RNA-bound heme, peroxidase activity, or complementation of ferrochelatase-deficient (heme H-) auxotrophs which could ultimately lead to in vivo complementation of ferrochelatase deficiency using gene transfer techniques.