Amino acids catalyse RNA formation under ambient alkaline conditions

Abstract

Abstract RNA and proteins are the foundation of life and a natural starting point to explore its origins. However, the prebiotic relationship between the two is asymmetric. While RNA evolved to assemble proteins from amino acids, a significant mirror-symmetric effect of amino acids to trigger the synthesis of RNA was missing. We describe ambient alkaline conditions where amino acids, without additional chemical activators, promote RNA copolymerisation more than 100-fold, starting from prebiotically plausible ribonucleoside-2′,3′-cyclic phosphates. The observed effect is explained by acid-base catalysis, with optimal efficiency at pH values near the amine pK aH. The fold-change in oligomerisation yield is nucleobase-selective, resulting in increased compositional diversity necessary for subsequent molecular evolution and favouring the formation of natural 3′−5′ linkages. The elevated pH offers recycling of oligonucleotide sequences back to 2′,3′-cyclic phosphates, providing conditions for high-fidelity replication by templated ligation. The findings reveal a clear functional role of amino acids in the evolution of RNA earlier than previously assumed.