6-thioguanosine and ribose-5-phosphate

Ribozymes (catalytic RNAs) were the center of a presumed RNA world in the early origin of life. In this issue, Lau and Unrau show evidence that an RNA world could have used a similar evolutionary pathway as most proteins do.

Topics: Evolution, Molecular; Guanosine; Nucleotides; Ribosemonophosphates; RNA, Catalytic; Thionucleosides

Here we report the in vitro selection of an unusual ribozyme that efficiently performs nucleotide synthesis even though it was selected to perform a distinctly different sugar chemistry. This ribozyme, called pR1, when derivatized with ribose 5-phosphate (PR) at its 3' terminus and incubated with 6-thioguanine, produces two interconverting thiol-containing products corresponding to a Schiff base and its Amadori rearranged product. Consistent with this hypothesis, removing the 2-hydroxyl from the PR substrate results in only a single product. Surprisingly, as this was not selected for, switching the tethered PR substrate to 5-phosphoribosyl 1-pyrophosphate results in the synthesis of 6-thioguanosine 5'-monophosphate. The discovery that a ribozyme can promote such distinct reactions spontaneously demonstrates that an RNA-mediated metabolism early in evolution could have evolved important new functionalities via ribozyme promiscuity.

Topics: Base Sequence; Guanosine; Kinetics; Molecular Sequence Data; Nucleotides; Ribosemonophosphates; RNA, Catalytic; Schiff Bases; Sulfhydryl Compounds; Thionucleosides