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Enzymatic RNA production from NTPs synthesized from nucleosides and trimetaphosphate V2.pdf (2.42 MB)

Enzymatic RNA Production from NTPs Synthesized from Nucleosides and Trimetaphosphate

revised on 15.02.2021, 18:47 and posted on 16.02.2021, 07:16 by Fabio Chizzolini, Alexandra Kent, Luiz F. M. Passalacqua, Andrej Lupták

A mechanism of nucleoside triphosphorylation would have been critical in an evolving “RNA world” to provide high-energy substrates for reactions such as RNA polymerization. However, synthetic approaches to produce ribonucleoside triphosphoates (rNTPs) have suffered from conditions such as high temperatures or high pH that lead to increased RNA degradation, as well as substrate production that cannot sustain replication. We demonstrate that cyclic trimetaphosphate (cTmp) can react with nucleosides to form rNTPs under mild, prebiotically-relevant conditions, with second-order rate constants ranging from 1.7 x 10–6 to 6.5 x 10–6 M–1 s–1. The ATP reaction shows a linear dependence on pH and Mg2+, and an enthalpy of activation of 88 ± 4 kJ/mol. At millimolar nucleoside and cTmp concentrations, the rNTP production rate is sufficient to facilitate RNA synthesis by both T7 RNA polymerase and a polymerase ribozyme. We suggest that the optimized reaction of cTmp with nucleosides may provide a viable connection between prebiotic nucleotide synthesis and RNA replication.


Email Address of Submitting Author


University of California, Irvine


United States of America

ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest

Version Notes

Revised rate constant units.

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