Enzyme-Free Copying of 12Bases of RNA with Dinucleotides

Gabrielle Leveau*, Daniel Pfeffer*, Bernhard Altaner, Eric Kervio, Franziska Welsch, Ulrich Gerland and Clemens Richert

Angewandte Chemie International Edition https://doi.org/10.1002/anie.202203067

Abstract

The synthesis of complementary strands is the reaction underlying the replication of genetic information. It is likely that the earliest self-replicating systems used RNA as genetic material. How RNA was copied in the absence of enzymes and what sequences were most likely to have supported replication is not clear. Here we show that mixtures of dinucleotides with C and G as bases copy an RNA sequence of up to 12 nucleotides in diluteaqueous solution. Successful enzyme-free copying occurred with in situactivation at 4 °C andpH 6.0. Dimers were incorporated in favor of monomers when both competed as reactants, and little misincorporation was detectable in mass spectra. Simulations using experimental rate constants confirmed that mixed C/G sequences are goodcandidates for successful replication with dimers. Because dimers are intermediates in the synthesis of longer strands, our results supportevolutionary scenariosencompassing formation and copying of RNA strandsin enzyme-free fashion.