Triplet-Encoded Prebiotic RNA Aminoacylation

• DOI: 10.1021/jacs.3c03931
• Publication Date: 2023-07-12T10:08:37Z
• Authors: Meng Su; Christian Schmitt; Ziwei Liu; Samuel J. Roberts; Kim C. Liu; Konstantin Röder; Andres Jäschke; David J. Wales; John D. Sutherland
• Keywords: Amino Acyl-tRNA Synthetases; Base Sequence; RNA, Transfer; Genetic Code; RNA; Nucleic Acid Conformation; Aminoacylation

AbstractThe 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 influence the chemoselectivity of aminoacylation by either route. For aminoacyl-transfer from a mixed anhydride donor strand, the chemoselectivity and stereoselectivity of aminoacylation depends on the terminal three base pairs of the stem. The results support early suggestions of a second genetic code in the acceptor stem.One-Sentence SummarySelectivity of RNA stem-overhang aminoacylation is controlled by the terminal trinucleotide sequence of the stem.