3 items with the tag “ribozyme

  • NAI ASTEP ASTID Exobiology Feature Stories

    The Ribozyme in Action

    March 15, 2010
  • Ironing Out the RNA World
    NAI 2011 Georgia Institute of Technology Annual Report

    Life originated during the early Archean, which was characterized by a non-oxidative atmosphere and abundant soluble Fe2+. Current theories on the origin of life focus on RNA-based genetic and metabolic systems. Here we show, by theory and experiment, that critical roles of Mg2+ in extant RNA folding and function can be better served by Fe2+ in the absence of oxygen. The results of our high-level quantum mechanical calculations show that the geometry of coordination of Fe2+ by RNA phosphates is similar to that of Mg2+. The conformation of Tetrahymena Group I intron P4-P6 domain is conserved between complexes of Fe2+ and Mg2+. Additionally, a ribozyme obtained previously by in vitro selection in the presence of Mg2+ and a natural ribozyme both have significantly greater catalytic competence in the presence of Fe2+ than in Mg2+. The combined biochemical and paleogeological data are consistent with an RNA-Fe2+ world that could have supported an array of RNA structures and catalytic functions far more diverse that of an RNA-Mg2+ world.

    ROADMAP OBJECTIVES: 4.1 4.2
  • Ironing Out the RNA World
    NAI 2012 Georgia Institute of Technology Annual Report

    In RNA World models of evolution, RNA was once the primary biopolymer of genetics and catalysis (1). Ancient RNA-based life would have inhabited an earth with abundant soluble iron and no free oxygen (2,3). Anoxic life persisted for around 1.0-1.5 billion years before photosynthesis began producing substantial free oxygen. The ‘great oxidation’ led to Fe2+/O2 mediated cellular damage (4) and depletion of soluble iron from the biosphere (5). We hypothesize that Fe22+ was an RNA cofactor when iron was benign and abundant and that Fe2+ was replaced by Mg2+ during the great oxidation. The RNA-Fe2+ to RNA-Mg2+ hypothesis is in close analogy with known metal substitutions in some metalloproteins (6-11). An ancestral ribonucleotide reductase (RNR), for example, spawned di-iron, di-manganese, and iron-manganese RNRs (12). Our hypothesis is supported by observations (13) that (i) RNA folding is conserved between complexes with Fe2+ and Mg2+ and (ii) at least some phosphoryl transfer ribozymes are more active in the presence of Fe2+ than Mg2+. Here, we demonstrate that reversing the putative metal substitution in an anoxic environment, by removing Mg2+ and adding Fe2+, expands the catalytic repertoire of some RNAs. Fe2+ can confer on RNA a previously uncharacterized ability to catalyze single electron transfer. Catalysis is specific, in that it is dependent on the type of RNA. The 23S rRNA and tRNA, some of the most abundant and ancient RNAs (14), are found to be efficient electron transfer ribozymes in the presence of Fe2+. Therefore, the catalytic competence of ancient RNAs may have been greater in early earth conditions than in extant conditions, and the experiments described here may be reviving latent function.

    ROADMAP OBJECTIVES: 4.1 4.2