The translation of messenger RNA sequences into polypeptide sequences according to the genetic code is central to life. How this process, which relies on the ribosomal machinery, arose from much simpler precursors is unclear. Here, we demonstrate that single nucleotides charged with an amino acid couple with amino acids linked to the 5′-terminus of an RNA primer in reactions directed by the nucleotides of an RNA template in dilute aqueous solution at 0 °C. When a mixture of U-Val, A-Gly and G-Leu competed for coupling to Gly-RNA, base pairing dictated which dipeptide sequence formed preferentially. The resulting doubly anchored dipeptides can retain their link to the primer for further extension or can be fully released under mild acidic conditions. These results show that a single-nucleotide-based form of translation exists that requires no more than oligoribonucleotides and anchored amino acids.
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We thank D. Pfeffer for help with high-performance liquid chromatography, H. Griesser for reading and commenting on a draft of the manuscript, E. Kervio and S. Lorenz for discussions, D. Göhringer for technical assistance and C. Guttroff for measuring ESI mass spectra. This work was funded by Deutsche Forschungsgemeinschaft (project-ID 364653263-TRR 235) and the Volkswagen Foundation (grant no. Az 92 768) (to C.R.).
The authors declare no competing interests.
Peer review information Nature Chemistry thanks Thomas Carell and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Jash, B., Tremmel, P., Jovanovic, D. et al. Single nucleotide translation without ribosomes. Nat. Chem. 13, 751–757 (2021). https://doi.org/10.1038/s41557-021-00749-4
Nature Chemistry (2021)