Triplet-Encoded Prebiotic RNA Aminoacylation
Meng Su, Christian Schmitt, Ziwei Liu, Samuel J. Roberts, Kim C. Liu, Konstantin Röder, Andres Jäschke*, David J. Wales*, and John D. Sutherland*
J. Am. Chem. Soc. https://doi.org/10.1021/jacs.3c03931
The encoding step of translation involves attachment of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases, themselves the product of coded peptide synthesis. So, the question arises─before these enzymes evolved, how were primordial tRNAs selectively aminoacylated? Here, we demonstrate enzyme-free, sequence-dependent, chemoselective aminoacylation of RNA. We investigated two potentially prebiotic routes to aminoacyl-tRNA acceptor stem-overhang mimics and analyzed those oligonucleotides undergoing the most efficient aminoacylation. Overhang sequences do not significantly influence the chemoselectivity of aminoacylation by either route. For aminoacyl-transfer from a mixed anhydride donor strand, the chemoselectivity and stereoselectivity of aminoacylation depend on the terminal three base pairs of the stem. The results support early suggestions of a second genetic code in the acceptor stem.