A Potential Role for Aminoacylation in Primordial RNA Copying Chemistry

Abstract

Aminoacylated tRNAs are the substrates for ribosomal protein synthesis in all branches of life, implying an ancient origin for aminoacylation chemistry. In the 1970s, Orgel and colleagues reported potentially prebiotic routes to aminoacylated nucleotides and their RNA templated condensation to form amino acid bridged dinucleotides. However, it is unclear whether such reactions would have aided or impeded nonenzymatic RNA replication. Determining whether aminoacylated RNAs could have been advantageous in evolution prior to the emergence of protein synthesis remains a key challenge. We therefore tested the ability of aminoacylated RNA to participate in both templated primer extension and ligation reactions. We find that at low magnesium concentrations that favor fatty acid-based protocells, these reactions proceed orders of magnitude more rapidly than when initiated from the cis-diol of unmodified RNA. We further demonstrate that amino acid bridged RNAs can act as templates in a subsequent round of copying. Our results suggest that aminoacylation facilitated nonenzymatic RNA replication, thus outlining a potentially primordial functional link between aminoacylation chemistry and RNA replication.Abstract Figure

Non-enzymatic assembly of active chimeric ribozymes from aminoacylated RNA oligonucleotides

“…To assess the activity of the chimeric hammerhead ribozyme, we modified the assembly process by using a DNA, rather than an RNA, template complementary to the full ribozyme sequence. We have previously found that DNase digestion of similar templates can be used to release pyrophosphate-linked (30) and amino acid-bridged (27) RNAs, and we reasoned that the same strategy would release the full-length chimeric ribozyme, allowing it to fold into the active conformation and bind its substrate (Figure S1C). Although not prebiotically relevant, this approach permitted a systematic assessment of the activity of chimeric ribozymes.…”

“…We assembled the chimeric ligase ribozyme using RNA oligonucleotides aminoacylated with L-lys because aminoacyl-RNA ligation with this amino acid resulted in the highest yields (Figure 3A, S5). (27) Our choice of L-lys was also informed by the observation that L-lys amino acid bridges were the most well tolerated within the hammerhead ribozyme (Figure 2 B, C). Despite containing three L-lys bridges in its backbone, the chimeric ligase ribozyme was functional, exhibiting half the activity of the corresponding all-RNA ribozyme (Figure 3B, C).…”

Prebiotic Chemistry in Aqueous Environment: A Review of Peptide Synthesis and Its Relationship with Genetic Code

“…[106][107][108] According to the "RNA world" hypothesis, chemical evolution prepares conditions for the emergence of life, prompting subsequent biological evolution. [109][110] Thus, chiral selection might result from some simple intrinsic chemical reaction in the prebiotic environment. A small initial imbalance of the amino acid enantiomers can promote the synthesis of highly enantioenriched RNA precursor from racemic starting materials.…”

“…A small initial imbalance of the amino acid enantiomers can promote the synthesis of highly enantioenriched RNA precursor from racemic starting materials. [ 111 ]…”

“…have utilized aminoacylated RNA to form other P—N species through templated primer extension and ligation reaction, which suggested that aminoacylation facilitated nonenzymatic RNA replication. [ 111 ] In the primitive molecular evolution, many P—N species might have existed. 5’‐aa‐AMPs (P—O species) as an activated form in the peptide synthesis is probably a later evolutionary product.…”