title: A promiscuous ribozyme promotes nucleotide synthesis in addition to ribose chemistry.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Matthew W L
authors.initials: MW
authors.lastname: Lau
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Unrau
mesh_terms: D001483:Base Sequence; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000096:biosynthesis*; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*; D012267:Ribosemonophosphates / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013872:Thionucleosides / Q000737:chemistry*
chemical_list: D009711:Nucleotides; D016337:RNA, Catalytic; D012267:Ribosemonophosphates; D012545:Schiff Bases; D013438:Sulfhydryl Compounds; D013872:Thionucleosides; D006151:Guanosine; C031626:ribose-5-phosphate; C005783:6-thioguanosine