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Open AccessHypothesis

RNA Catalysis, Thermodynamics and the Origin of Life

Department of Chemistry and Biochemistry, and The Center for the Molecular Biology of RNA, University of California at Santa Cruz, Santa Cruz, CA 95064, USA
Lawrence Livermore National Laboratory, Livermore, CA 94551, USA
Department of Chemistry, Cabrillo College, 6500 Soquel Drive, Aptos, CA 95003, USA
Author to whom correspondence should be addressed.
Life 2014, 4(2), 131-141;
Received: 27 February 2014 / Revised: 28 March 2014 / Accepted: 31 March 2014 / Published: 10 April 2014
(This article belongs to the Special Issue The Origins and Early Evolution of RNA)
The RNA World Hypothesis posits that the first self-replicating molecules were RNAs. RNA self-replicases are, in general, assumed to have employed nucleotide 5ʹ-polyphosphates (or their analogues) as substrates for RNA polymerization. The mechanism by which these substrates might be synthesized with sufficient abundance to supply a growing and evolving population of RNAs is problematic for evolutionary hypotheses because non-enzymatic synthesis and assembly of nucleotide 5ʹ-triphosphates (or other analogously activated phosphodiester species) is inherently difficult. However, nucleotide 2ʹ,3ʹ-cyclic phosphates are also phosphodiesters, and are the natural and abundant products of RNA degradation. These have previously been dismissed as viable substrates for prebiotic RNA synthesis. We propose that the arguments for their dismissal are based on a flawed assumption, and that nucleotide 2ʹ,3ʹ-cyclic phosphates in fact possess several significant, advantageous properties that indeed make them particularly viable substrates for prebiotic RNA synthesis. An RNA World hypothesis based upon the polymerization of nucleotide 2ʹ,3ʹ-cyclic phosphates possesses additional explanatory power in that it accounts for the observed ribozyme “fossil record”, suggests a viable mechanism for substrate transport across lipid vesicle boundaries of primordial proto-cells, circumvents the problems of substrate scarcity and implausible synthetic pathways, provides for a primitive but effective RNA replicase editing mechanism, and definitively explains why RNA, rather than DNA, must have been the original catalyst. Finally, our analysis compels us to propose that a fundamental and universal property that drives the evolution of living systems, as well as pre-biotic replicating molecules (be they composed of RNA or protein), is that they exploit chemical reactions that already possess competing kinetically-preferred and thermodynamically-preferred pathways in a manner that optimizes the balance between the two types of pathways. View Full-Text
Keywords: ribozymes; RNA self-replication; RNA world; nucleotide 2ʹ,3ʹ-cyclic phosphates; RNA polymerization ribozymes; RNA self-replication; RNA world; nucleotide 2ʹ,3ʹ-cyclic phosphates; RNA polymerization
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Scott, W.G.; Szöke, A.; Blaustein, J.; O'Rourke, S.M.; Robertson, M.P. RNA Catalysis, Thermodynamics and the Origin of Life. Life 2014, 4, 131-141.

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