According to the RNA world hypothesis, 4 RNA was the first biological macromolecule to appear in the prebiotic environment. It is capable of both storing genetic information and catalysing essential biochemical reactions. Given RNA's key role in the synthesis of proteins there has been a long-standing interest in understanding how translation developed on early Earth. Several cases of RNA-catalysed/mediated peptide synthesis have been reported. A 196-nt ribozyme was evolved to perform a peptidyl transfer reaction to yield Met-Phe dipeptide. 5,6 A triphenylalanyl-RNA ester was formed in a nicked RNA/DNA duplex without additional ribozymes. Oligophenylalanine up to a pentapeptide was detected using a five-nucleotide ribozyme and phenylalanyl adenosine monophosphate. Interestingly, in all these cases the amino acids studied are not considered prebiotically plausible. Crucially, no relationship between RNA sequence and peptide sequence has been demonstrated with these systems. Two examples of RNA-templated peptide synthesis, in a nicked duplex or across a duplex terminus, were published recently. 12,13 A condensation buffer containing carbodiimide (EDC) or 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM) was required in either case, thus, the coupling reactions are not spontaneous. Furthermore, an adequate hypothesis for how either of these mechanisms could have transitioned to the extant mechanism is yet to be proposed, calling into question their relevance to the origin and early evolution of life.