RNA world theories feature prominently in origins-of-life models, which propose that RNA or a similar polymer played major roles in biological catalysis, in addition to storing heritable genetic…

This is a $4,988,047.00 grant awarded by the National Aeronautics and Space Administration (NASA) to the University of Missouri System to conduct research on the potential for RNA to sustain cellular metabolism and serve as a bridge between bottom-up and top-down approaches to RNA world research. The research aims to address a critical missing piece in RNA world theories by exploring the emergence of robust, catalytic ribozymes as precursors to contemporary metabolic pathways. The project brings together a team of 12 faculty members from 8 institutions with expertise in relevant fields. This grant supports NASA's objectives related to the PCE3 and FECM research coordination networks. The contract does not have a set-aside designation.

RNA world theories feature prominently in origins-of-life models, which propose that RNA or a similar polymer played major roles in biological catalysis, in addition to storing heritable genetic information. While some RNA world elements are well supported by experimental data, the biological viability of such ribo-organisms remains speculative or requires extrapolation well beyond the existing data. In particular, IT is well-established that RNA can promote several classes of chemical reactions in single-turnover format with non-biological substrates, but IT is unknown whether RNA can provide the necessary catalysis to support complex cellular functions, or how such catalysts might emerge. Indeed, the dearth of robust RNA catalysts for small molecule transformation is the single biggest bottleneck in the construction of model ribo-organisms. A long-term goal of our consortium is to define the potential of RNA to sustain cellular metabolism and to fully bridge the GAP between bottom-up and top-down approaches to RNA world research, thereby touching on both the PCE3 and fecm research collaborative networks (rcns). The proposed research will provide experimental underpinning to a critical missing piece of the RNA world puzzle: emergence of robust, truly catalytic, multiple turnover ribozymes as precursors to contemporary metabolic pathways. Methods/techniques/approach: the team comprises 12 faculty from 8 institutions, with expertise in RNA biochemistry, structural biology, enzymology, ribozyme selection, synthetic organic chemistry, bacteriology, synthetic biology, systems biology modeling, and informatics of evolving RNA populations. Relevance to NASA objectives: an RNA world could provide a bridge between bottom-up and top-down approaches that are at the heart of the PCE3 and fecm research coordination networks.