High-yield prebiotic polymerization of 2’,3’-cyclic nucleotides under wet-dry cycling

The spontaneous formation of RNA polymers is one of the most crucial yet unsolved steps in the investigation of the origin of life. RNA oligomerization from nucleotide solutions has so far been reported only with low reactivity. Here we show that 2’,3’-cyclic nucleotides of all four nucleobases efficiently polymerize without external activators when dehydrated at room temperature in a mild alkaline pH range. Oligomerization yield, Y, and the polymer length further increase by wet-dry cycling, peaking at Y ≈ 70% in guanosine solutions and Y ≥ 20% for the other nucleobases when individually solubilized. Microscopy observation during drying indicates that the guanosine reactivity is enhanced over the other nucleobases by its self-assembly propensity. We show that at pH 11, a condition disfavoring guanosine structuring, polymerization in stoichiometrically balanced solution of the four nucleotides reaches Y = 36% and well distributed inclusion of nucleobases in the chains. The simplicity of the procedure, where only water is added at each cycle, makes this process a promising candidate for the prebiotic origin of RNA oligomers on early Earth.