Primitive RNA-catalysis with guanine-rich oligonucleotide sequences – the case of a (GGC)₃nonamer

Abstract

A cornerstone of molecular evolution leading to the emergence of life on our planet is associated with appearance of the first catalytic RNA molecules. A question remains regarding the nature of the simplest catalytic centers that could mediate the chemistry needed for RNA-catalysis. In the current paper we provide a new example supporting our previously suggested model proposing that transiently formed open loop geometries could serve as temporary catalytic sites in the most ancient short oligonucleotides. In particular, using two independent detection techniques, PAGE and MALDI-ToF analysis, we show that prolonged thermal treatment of a 5'-phosphorylated (GGC)3 sequence at weakly acidic or neutral pH in the presence of tris(hydroxymethyl)aminomethane, produces a species characterized by a (GGC)3G stoichiometry, which is compatible with the cleavage-terminal recombination chemistry suggested in our previous studies. Our new findings are complemented by microsecond-scale molecular dynamics simulations, showing that (GGC)3 dimers readily sample transient potentially catalytic geometries compatible with the experimentally observed terminal recombination chemistry.