title: Self-incorporation of coenzymes by ribozymes.
abstract: RNA molecules that are assembled from the four standard nucleotides contain a limited number of chemical functional groups, a characteristic that is generally thought to restrict the potential for catalysis by ribozymes. Although polypeptides carry a wider range of functional groups, many contemporary protein-based enzymes employ coenzymes to augment their capabilities. The coenzymes possess additional chemical moieties that can participate directly in catalysis and thereby enhance catalytic function. In this work, we demonstrate a mechanism by which ribozymes can supplement their limited repertoire of functional groups through RNA-catalyzed incorporation of various coenzymes and coenzyme analogues. The group I ribozyme of Tetrahymena thermophila normally mediates a phosphoester transfer reaction that results in the covalent attachment of guanosine to the ribozyme. Here, a shortened version of the ribozyme is shown to catalyze the self-incorporation of coenzymes and coenzyme analogues, such as NAD+ and dephosphorylated CoA-SH. Similar ribozyme activities may have played an important role in the "RNA world," when RNA enzymes are thought to have maintained a complex metabolism in the absence of proteins and would have benefited from the inclusion of additional functional groups.
authors.affiliation: Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Breaker
authors.forename: G F
authors.initials: GF
authors.lastname: Joyce
mesh_terms: D000818:Animals; D003067:Coenzymes / Q000378:metabolism*; D006151:Guanosine / Q000378:metabolism; D007438:Introns; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D016337:RNA, Catalytic / Q000378:metabolism*; D013379:Substrate Specificity; D016808:Tetrahymena thermophila / Q000201:enzymology
chemical_list: D003067:Coenzymes; D016337:RNA, Catalytic; D009243:NAD; D006151:Guanosine; D009249:NADP