UC San Diego

An early stage of life likely used catalytic RNAs (ribozymes) to support self-replication and a metabolism. Because the abiotic polymerization of RNA is challenging, the formation of long RNA polymers is unlikely on the prebiotic Earth. In addition, ribozymes likely co-evolved with peptides since the formation of amino acids under prebiotic conditions occurs readily and peptide bond formation occurs under prebiotic conditions. Like in today's organisms, nucleoside 5ʹ-triphosphates (NTPs) may have been used as central building blocks for self-replication and in metabolism. In early stages of life, NTPs could have been generated by reacting nucleoside 5ʹ-hydroxyl groups with the prebiotically plausible molecule cyclic trimetaphosphate (cTmp). Our lab previously showed that this chemistry can be catalyzed by ribozymes, but these ribozymes generated only RNA 5ʹ-triphosphates and not free NTPs. In this work, a combinatorial method that can be used to identify short catalytic motifs from pools of active ribozymes is demonstrated. Diamidophosphate is investigated as an alternative reactive phosphorus species to generate NTPs and it is shown that ribozymes can use NTPs from this reaction. A ribozyme capable of synthesizing GTP from cTmp and guanosine is characterized. And finally, a novel interaction between a prebiotically plausible peptide and a self-triphosphorylating ribozyme is identified and characterized.