title: Control of gene expression by a natural metabolite-responsive ribozyme.
abstract: Most biological catalysts are made of protein; however, eight classes of natural ribozymes have been discovered that catalyse fundamental biochemical reactions. The central functions of ribozymes in modern organisms support the hypothesis that life passed through an 'RNA world' before the emergence of proteins and DNA. We have identified a new class of ribozymes that cleaves the messenger RNA of the glmS gene in Gram-positive bacteria. The ribozyme is activated by glucosamine-6-phosphate (GlcN6P), which is the metabolic product of the GlmS enzyme. Additional data indicate that the ribozyme serves as a metabolite-responsive genetic switch that represses the glmS gene in response to rising GlcN6P concentrations. These findings demonstrate that ribozyme switches may have functioned as metabolite sensors in primitive organisms, and further suggest that modern cells retain some of these ancient genetic control systems.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520-8103, USA.
authors.forename: Wade C
authors.initials: WC
authors.lastname: Winkler
authors.forename: Ali
authors.initials: A
authors.lastname: Nahvi
authors.forename: Adam
authors.initials: A
authors.lastname: Roth
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Collins
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Breaker
mesh_terms: D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D004789:Enzyme Activation; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
chemical_list: D001426:Bacterial Proteins; D005944:Glucosamine; D019298:Glucose-6-Phosphate; D012329:RNA, Bacterial; D016337:RNA, Catalytic; C001293:glucosamine 6-phosphate; C000731191:component S, glutamate mutase protein, Bacteria; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)