A Potential Role for Aminoacylation in Primordial RNA Copying Chemistry

Biochemistry. 2021 Feb 16;60(6):477-488. doi: 10.1021/acs.biochem.0c00943. Epub 2021 Feb 1.

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 non-enzymatic 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 non-enzymatic RNA replication, thus outlining a potentially primordial functional link between aminoacylation chemistry and RNA replication.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aminoacylation / physiology
  • Dinucleoside Phosphates / metabolism
  • Nucleic Acid Conformation
  • Nucleotides / metabolism
  • RNA / metabolism
  • Templates, Genetic
  • Transfer RNA Aminoacylation / genetics
  • Transfer RNA Aminoacylation / physiology*

Substances

  • Dinucleoside Phosphates
  • Nucleotides
  • RNA