RNA Folding and Catalysis Mediated by Iron (II)

Mg(2+) shares a distinctive relationship with RNA, playing important and specific roles in the folding and function of essentially all large RNAs. Here we use theory and experiment to evaluate Fe(2+) in the absence of free oxygen as a replacement for Mg(2+) in RNA folding and catalysis. We describe both quantum mechanical calculations and experiments that suggest that the roles of Mg(2+) in RNA folding and function can indeed be served by Fe(2+). The results of quantum mechanical calculations show that the geometry of coordination of Fe(2+) by RNA phosphates is similar to that of Mg(2+). Chemical footprinting experiments suggest that the conformation of the Tetrahymena thermophila Group I intron P4–P6 domain RNA is conserved between complexes with Fe(2+) or Mg(2+). The catalytic activities of both the L1 ribozyme ligase, obtained previously by in vitro selection in the presence of Mg(2+), and the hammerhead ribozyme are enhanced in the presence of Fe(2+) compared to Mg(2+). All chemical footprinting and ribozyme assays in the presence of Fe(2+) were performed under anaerobic conditions. The primary motivation of this work is to understand RNA in plausible early earth conditions. Life originated during the early Archean Eon, characterized by a non-oxidative atmosphere and abundant soluble Fe(2+). The combined biochemical and paleogeological data are consistent with a role for Fe(2+) in an RNA World. RNA and Fe(2+) could, in principle, support an array of RNA structures and catalytic functions more diverse than RNA with Mg(2+) alone.