Mineral-Promoted RNA Polymerization: Investigating Structural Properties of Catalytic Minerals

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The goal of the proposed work is to identify minerals which could have played a role in the origin of life (OoL) on early Earth by promoting the formation of longer molecules (polymers) of ribonucleic acid (RNA) from simple starting precursor molecules (monomers). Before life and enzymes, it is proposed that minerals may have acted as catalysts to play the role of enzymes in promoting polymerization. RNA is one of the most important molecules in biology because of its ability to play many roles. In the OoL, the formation of polymers is important because oligomers have the ability to take on different structures and functionalities. Thus, polymerization of monomers is a key bridging step in the progress from simple organic precursors towards the earliest life-like cells. The proposed work would contribute to NSF's goal of promoting the progress of fundamental science in one of the most profound questions asked by humankind, which is, how did life begin? The proposed work also includes numerous outreach activities, including the development of a weekly program on National Public Radio as well as a public science lecture series, which would bring science to the general public, and outreach activities to encourage women and diversity. The grant funds would support a post-doctoral researcher. Thus, the proposed work also supports NSF's goal of supporting education and diversity, and training the future scientific workforce.Minerals, because of their reactivity and ubiquity, likely contributed to the origin of life in the transformation from prebiotic geochemistry to biochemistry. RNA is an information- carrier and some RNAs can also act as enzymes, so RNA is believed to have been a precursor to DNA and enzymes in the origins of life. One of the major challenges in the field is the non-enzymatic (prebiotic) synthesis of RNA oligomers, and minerals have long been proposed as prebiotic catalysts. The role of montmorillonite in promoting polymerization of activated ribonucleotides in the presence of magnesium or high concentrations of alkali cations has been known for thirty years, and several studies have investigated RNA monomer adsorption on minerals, but other catalytic minerals are not known. Thus, there is a lack of knowledge about any potential relationships between mineral structure and polymerization catalytic efficiency. We propose to address this gap in our knowledge. We propose three hypotheses for the relationship between the mineral structure, its adsorption capacity and its catalytic efficiency: (1) adsorbed ribonucleotide conformation is more important than adsorption capacity of the mineral for catalysis; (2) the divalent or alkali cations should form outer-sphere ternary complexes between the nucleotide and any negatively charged mineral surface, so that they can be easily displaced and the nucleotide phosphate is still available for phosphorylation; and (3) the mineral should provide a nanoconfined environment where the condensation reaction can occur despite bulk aqueous environment. Specific minerals, such as birnessite, hydrotalcite and zeolites are predicted to have catalytic structures. The broad goals of the present study are to shed light on any potential relationships between mineral structure, surface chemistry, adsorption capacity, adsorbed conformation and polymerization efficiency, thus, discovering new catalytic minerals. The specific aims are (1) to determine the adsorption characteristics of adenosine monophosphate nucleotides in the absence and presence of dissolved cations;(2) to determine the nucleotide polymerization-promoting ability of various minerals; (3) to determine the detailed molecular-level conformation of adsorbed mononucleotides on minerals that promote polymerization; and (4) to synthesize these results to develop a model for explaining the catalytic ability of montmorillonite and to test the predicted catalytic activity of specific minerals. We will determine adsorption using UV-Vis spectrophotometry, and polymerization of mononucleotides on the known catalytic mineral and on the newly predicted minerals by High Performance Liquid Chromatography (HPLC) and MALDI-TOF Mass Spectrometry. Conformation of adsorbed monomer will be determined by Magic Angle Spinning NMR spectroscopy and by Fourier Transform Infra-Red Spectroscopy. The proposed work provides structure-based predictions for catalytic activity, thus helping to identify new catalytic minerals beyond montmorillonite. Knowledge of a wider variety of catalytic minerals under specific environmental conditions will help predict the plausibility of prebiotic polymerization reactions of biomolecules for life's emergence on other solid worlds, e.g., Mars.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.