Ribosomal translation at the origin of life requires controlled aminoacylation to produce mono-aminoacyl esters of tRNAs. Herein, we show that transient annealing of short RNA oligo:amino acid mixed anhydrides to an acceptor strand enables the sequential transfer of aminoacyl residues to the diol of an overhang, first forming aminoacyl esters then peptidyl esters. Using N-protected aminoacyl esters prevents unwanted peptidyl ester formation in this manner. However, N-acyl-aminoacyl transfer is not stereoselective.
The Central Dogma dominates our understanding of modern biology. However, the mechanisms of how RNA directed peptide synthesis (translation) developed at the dawn of life remain a puzzle. In this study, we demonstrate that short peptides can spontaneously form at the end of a duplex RNA with an overhang. Contemporary proteins are composed exclusively of L-amino acids and our research reveals that L-amino acids with free amino groups are also more likely to participate in this prebiotic peptide synthesis mechanism. Conversely, when one of the amino acids is protected as it is in modern bacteria, this preference disappears. We demonstrate this chemistry can afford a variety of peptide sequences in a sequence-dependent manner.
© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.