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Updated: Jul 23, 2025

Chemical Triphosphorylation of Oligonucleotides
Published on: June 2, 2022
Triplet-Encoded Prebiotic RNA Aminoacylation
Meng Su1, Christian Schmitt2, Ziwei Liu1
1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
None:
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.
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