title: A thiamin-utilizing ribozyme decarboxylates a pyruvate-like substrate.
abstract: Vitamins are hypothesized to be relics of an RNA world, and were probably participants in RNA-mediated primordial metabolism. If catalytic RNAs, or ribozymes, could harness vitamin cofactors to aid their function in a manner similar to protein enzymes, it would enable them to catalyse a much larger set of chemical reactions. The cofactor thiamin diphosphate, a derivative of vitamin B1 (thiamin), is used by enzymes to catalyse difficult metabolic reactions, including decarboxylation of stable α-keto acids such as pyruvate. Here, we report a ribozyme that uses free thiamin to decarboxylate a pyruvate-based suicide substrate (LnkPB). Thiamin conjugated to biotin was used to isolate catalytic individuals from a pool of random-sequence RNAs attached to LnkPB. Analysis of a stable guanosine adduct obtained via digestion of an RNA sequence (clone dc4) showed the expected decarboxylation product. The discovery of a prototypic thiamin-utilizing ribozyme has implications for the role of RNA in orchestrating early metabolic cycles.
authors.affiliation: Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Cernak
authors.forename: Dipankar
authors.initials: D
authors.lastname: Sen
mesh_terms: D001710:Biotin / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D011767:Pyruvate Decarboxylase / Q000737:chemistry* / Q000378:metabolism; D011773:Pyruvates / Q000737:chemistry* / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism; D013831:Thiamine / Q000737:chemistry* / Q000378:metabolism; D013835:Thiamine Pyrophosphate / Q000737:chemistry / Q000378:metabolism
chemical_list: D011773:Pyruvates; D016337:RNA, Catalytic; D001710:Biotin; D011767:Pyruvate Decarboxylase; D013835:Thiamine Pyrophosphate; D013831:Thiamine