5′ RNA Aminoacylation via Interstrand Acyl-Transfer

The catalytic transformations driving coded protein synthesis revolve around linkage of amino acids to molecules of RNA as 2’/3′-aminoacyl esters. This defining molecular species of life is installed, supervised and utilised by complex catalysts, but its relative hydrolytic lability limits its accumulation and behaviour during the early development of the translation system in a simpler RNA-based biology. Herein, we describe a rapid catalytic transfer reaction inherent to RNA duplexes that establishes a more stable RNA-amino acid linkage. We observe spontaneous aminoacyl transfer from the 2’/3′-hydroxyl of a donor oligonucleotide to the 5′-hydroxyl of an adjacent template-bound acceptor oligonucleotide. In RNA systems dominated by base pairing, this transfer drives selective accumulation of the more stable 5′-aminoacyl RNA in the presence of a prebiotically-plausible aminoacylation reagent. This catalytic context could shape the distribution of aminoacylation amongst prebiotic RNAs and open opportunities for simple forms of RNA-directed peptide synthesis.