Origins of RNA Catalysis in Extreme Environments

Somagenics Incorporated, Santa Cruz CA

Investigators

Abstract

0085627 Brian Johnston This project explores the idea that extreme environmental conditions such as freezing and dehydration could be vital forces in the emergence of life from a prebiotic world containing RNA. The idea is based on the discovery that such conditions can stimulate a key synthetic reaction (self-ligation) in a small, virus-associated, modern, catalytic RNA. The discovery of RNA catalysis inspired the concept dubbed the RNA-world hypothesis, which maintains that early in the evolution of life, both information-carrying and catalytic functions of self-replicating entities were provided by RNA. However, the susceptibility of the RNA backbone to chemical cleavage, particularly in the presence of the divalent metal ions that are the normal cofactors for RNA catalysis, challenges whether RNA could ever have developed enough complexity to become functionally useful in the absence of the protective environment of the cell. The P.I.'s laboratory recently discovered that the hairpin ribozyme (HPR) catalyzes efficient ligation in the absence of metal ion cofactors when solutions of the HPR are subjected to freezing and/or dehydration. This discovery led to speculating whether dehydration-induced ligation could have played a role in building up RNA complexity in prebiotic evolution. Several facts support this conjecture: (1) Since their chemistries are the same, ligation provides a means of reversing random cleavage; (2) Freezing and dehydration can provide important mechanisms for concentrating and stabilizing macromolecules; and (3) Freezing and dehydrating environmental conditions are very likely to have existed on the early Earth. Moreover, such conditions are likely to exist or to have existed on Mars and Europa, two possible candidates for bearing extraterrestrial life. (Europa is believed to contain large amounts of freezing water, and Mars appears to have had flowing water in the past, possibly quite recently.) This conjecture would be strengthened if RNA structures in addition to HPR were found to have similar freezing- or dehydration-induced catalytic activity. Therefore the authors will investigate the likelihood that enzymatic capabilities conducive to the emergence of life can arise from those extreme conditions, by searching a random library of RNA sequences for new motifs that catalyze ligation of RNA under those conditions. An established selection protocol will be used, but only those sequences whose catalytic activity is induced by either freezing or chemical dehydration will be chosen. Successfully isolating and characterizing new families of such sequences will enhance our understanding of the mechanisms of RNA catalysis, provide important support for the origin of life in extreme environments, and invite searches for extremophiles that use such activities. This project will be a collaboration between Somagenics, Inc. and Princeton University, and will include a training component involving a graduate student and a post-doctoral fellow. As a company applying RNA technology to functional genomics, therapeutics, and diagnostics, Somagenics wishes to exploit special properties of RNA that emerge under unusual and extreme conditions.