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Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2022)

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.

    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2024)
    Catalytic RNAs (ribozymes) were central to early stages of life on earth. The first ribozymes probably emerged in the presence of prebiotically generated peptides because amino acids can be generated under abiotic conditions, and amino acids can oligomerize into peptides under prebiotically plausible conditions. Here we tested whether the presence of prebiotically plausible peptides could have aided the emergence of ribozymes, by an in vitro selection of self-triphosphorylation ribozymes from random sequence in the presence of ten different octapeptides. These peptides were composed of ten different, prebiotically plausible amino acids, each as mixture of d- and l-stereoisomers. After five rounds of selection and high throughput sequencing analysis, ten ribozymes that appeared most promising for peptide benefits were tested biochemically for possible benefits from each of the ten peptides. The strongest peptide benefit enhanced ribozyme activity by 2.6-fold, similar to the effect from an increase in the pH by one-half unit. Four arbitrarily chosen ribozymes from a previous selection without peptides showed no significant change in their activity in the presence of the ten peptides. Therefore, the used prebiotically plausible peptides - peptides without evolutionarily optimized sequence, without cationic or aromatic side chains - did not provide a strong benefit for the emergence of ribozyme activity. This finding stands in contrast to previously identified polycationic peptides, conjugates between peptides and polyaromatic hydrocarbons, and modern mRNA encoded proteins, all of which can strongly increase ribozyme function. The results are discussed in the context of origins of life.
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