RNA Oligomerisation without Added Catalyst from 2′,3′‐Cyclic Nucleotides by Drying at Air‐Water Interfaces**

Abstract

For the emergence of life, the abiotic synthesis of RNA from its monomers is a central step. We found that in alkaline, drying conditions in bulk and at heated air‐water interfaces, 2′,3′‐cyclic nucleotides oligomerised without additional catalyst, forming up to 10‐mers within a day. The oligomerisation proceeded at a pH range of 7–12, at temperatures between 40–80 °C and was marginally enhanced by K+ ions. Among the canonical ribonucleotides, cGMP oligomerised most efficiently. Quantification was performed using HPLC coupled to ESI‐TOF by fitting the isotope distribution to the mass spectra. Our study suggests a oligomerisation mechanism where cGMP aids the incorporation of the relatively unreactive nucleotides C, A and U. The 2′,3′‐cyclic ribonucleotides are byproducts of prebiotic phosphorylation, nucleotide syntheses and RNA hydrolysis, indicating direct recycling pathways. The simple reaction condition offers a plausible entry point for RNA to the evolution of life on early Earth.

A heated rock crack captures and polymerizes primordial DNA and RNA

“…48 For RNA, we studied the recently established polymerization from 2′,3′-cyclic RNA monomers. 14 This chemistry was studied in the past for AMP with the help of various catalysts. 9,15 Only recently, it was found that 2′,3′-cGMP itself can trigger oligomerization in the dry at elevated pH without ions or added catalysts, 14 then leading the way to copolymerization with other bases.…”

“…14 This chemistry was studied in the past for AMP with the help of various catalysts. 9,15 Only recently, it was found that 2′,3′-cGMP itself can trigger oligomerization in the dry at elevated pH without ions or added catalysts, 14 then leading the way to copolymerization with other bases. Possibly aided by the G-base in a yet unknown stacking arrangement, the 5′-hydroxyl attacks the 2′,3′-cyclic phosphate and leads to the opening of the phosphate ring either at the 2′- or the 3′-oxygen of the sugar.…”

“…Chemical mechanisms have been found that enable de novo strand formation from activated RNA monomers: 7–9 imidazole-activated RNA molecules 10–13 and 2′,3′-cyclic RNA monomers. 9,14,15…”

“…DNA nucleotides have been shown in other works 4–6 to form under relevant conditions and have been hypothesized to consequently have evolved at an early stage. The other polymerization chemistry of this study uses 2′,3′-cyclic RNA nucleotides, 9,14,15 with experimental protocols based on previous experiments using 3′,5′-cyclic GMP. 16,17 The polymerization of 2′,3′-cyclic RNA nucleotides takes place under dry conditions at elevated pH.…”

Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment

“…In conclusion, the data presented suggest that the heated airwater interface (AWI) system has the potential to host fragmented RNA replicators that catalyze both general and autocatalytic templatedirected RNA synthesis, further strengthening the hypothesis that dynamic, non-equilibrium environments were cradles for the emergence of higher order biomolecular complexity. Intriguingly, similar interface settings can drive other prebiotically relevant key processes such as the phosphorylation of mononucleosides, polymerization of RNA, encapsulation of nucleic acids in membrane vesicles as well as the fusion and fission of coacervate-based protocells 20,23,29,30 . Future work might explore the suitability of AWI-systems to combine these key aspects of biological systems into a single collective scenario providing a setting that could potentially support most, if not all, of the required capabilities for an inanimate system to adopt life-like behaviors.…”