Interstrand Aminoacyl Transfer in a tRNA Acceptor Stem-Overhang Mimic

J Am Chem Soc. 2021 Aug 4;143(30):11836-11842. doi: 10.1021/jacs.1c05746. Epub 2021 Jul 20.

Abstract

Protein-catalyzed aminoacylation of the 3'-overhang of tRNA by an aminoacyl-adenylate could not have taken place prior to the advent of genetically coded peptide synthesis, and yet the latter process has an absolute requirement for aminoacyl-tRNA. There must therefore have been an earlier nonprotein-catalyzed means of generating aminoacyl-tRNA. Here, we demonstrate efficient interstrand aminoacyl transfer from an aminoacyl phosphate mixed anhydride at the 5'-terminus of a tRNA acceptor stem mimic to the 2',3'-diol terminus of a short 3'-overhang. With certain five-base 3'-overhangs, the transfer of an alanyl residue is highly stereoselective with the l-enantiomer being favored to the extent of ∼10:1 over the d-enantiomer and is much more efficient than the transfer of a glycyl residue. N-Acyl-aminoacyl residues are similarly transferred from a mixed anhydride with the 5'-phosphate to the 2',3'-diol but with a different dependence of efficiency and stereoselectivity on the 3'-overhang length and sequence. Given a prebiotically plausible and compatible synthesis of aminoacyl phosphate mixed anhydrides, these results suggest that RNA molecules with acceptor stem termini resembling modern tRNAs could have been spontaneously aminoacylated, in a stereoselective and chemoselective manner, at their 2',3'-diol termini prior to the onset of protein-catalyzed aminoacylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacylation
  • Nucleic Acid Conformation
  • RNA, Transfer / chemistry
  • RNA, Transfer / metabolism*

Substances

  • RNA, Transfer