Amino acids catalyze RNA formation under ambient alkaline conditions

RNA and proteins are the core molecules of life. The sequence of mRNA encodes the protein sequence and proteins orchestrate the replication of nucleic acids. How this synergistic relationship arose remains an unanswered question. Amino acids have not yet provided an evolutionary advantage to nucleic acid synthesis. This relationship has been assumed as a late development during RNA evolution. Here we show that amino acids substantially improve the yield of RNA polymerization from prebiotically plausible ribonucleoside-2',3'-cyclic phosphates. The amino acid catalysis of RNA polymerization was base-selective, increased the compositional oligomer sequence diversity and favoured the formation of natural 3',5' linkages. It was most efficient at pH values close to the pKaH of the amines and correlated with sidechain hydrophobicities, suggesting a general acid-base mechanism akin to ribozyme-catalysed RNA-hydrolysis. This is confirmed by the observed general base-enhanced polymerization of G and U nucleotides. The copolymerization of G/C/A/U with valine resulted in a substantially increased oligomer yield and compositional diversity. The catalytic effect of proteinogenic amino acids on RNA oligomerization suggests the reactivity of amino acids and RNA was united earlier than previously thought, and their association likely predates the genetic code.