Triplet-encoded prebiotic RNA aminoacylation

Author:

Su MengORCID,Schmitt ChristianORCID,Liu Ziwei,Roberts Samuel J.ORCID,Liu Kim C.ORCID,Röder KonstantinORCID,Jäschke AndresORCID,Wales David J.,Sutherland John D.ORCID

Abstract

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.

Publisher

Cold Spring Harbor Laboratory

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