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bioRxiv · 10.1101/2023.03.13.532408

Triplet-encoded prebiotic RNA aminoacylation

Su, M.·Schmitt, C.·Liu, Z.·Roberts, S. J.·Liu, K. C.·Roder, K.·Jaschke, A.·Wales, D.·Sutherland, J. D.
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Abstract

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 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.

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Su, M., Schmitt, C., Liu, Z., Roberts, S. J., Liu, K. C., Roder, K., Jaschke, A., Wales, D., Sutherland, J. D.. 2023-03-13. Triplet-encoded prebiotic RNA aminoacylation. https://doi.org/10.1101/2023.03.13.532408

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