title: Coenzyme B12 riboswitches are widespread genetic control elements in prokaryotes.
abstract: Recent studies have begun to reveal that numerous fundamental metabolic pathways in bacteria are regulated by riboswitches residing within certain messenger RNAs. These riboswitches selectively bind metabolites and modulate gene expression in response to changing ligand concentrations. Previously, we provided evidence that the btuB mRNAs of Escherichia coli and Salmonella typhimurium each carry a coenzyme B12-dependent riboswitch that causes repressed translation of the encoded cobalamin-transport protein at elevated coenzyme concentrations. Herein, we use a phylogenetic analysis to define a consensus sequence and secondary structure model for the ligand- binding domain of this riboswitch class. RNA structures that conform to this model are widespread in both Gram-positive and Gram-negative organisms. In addition, we find that the 5'-untranslated region (5'-UTR) of the cobalamin biosynthesis (cob) operon of S.typhimurium carries an RNA motif that matches this consensus sequence. Biochemical and genetic characterization of this motif confirms that the RNA directly binds coenzyme B12, and that it likely serves as a genetic control element for regulating expression of the 25-gene operon for cobalamin production in this pathogen.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, P.O. Box 208103, New Haven, CT 06520-8103, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Nahvi
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Barrick
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Breaker
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001412:Bacillus subtilis / Q000235:genetics; D001483:Base Sequence; D003038:Cobamides / Q000096:biosynthesis / Q000378:metabolism*; D016384:Consensus Sequence / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics*; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009876:Operon / Q000235:genetics; D010802:Phylogeny; D011387:Prokaryotic Cells / Q000378:metabolism; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D013816:Thermodynamics
chemical_list: D020121:5' Untranslated Regions; D003038:Cobamides; D008024:Ligands; D012329:RNA, Bacterial; D038621:Regulatory Sequences, Ribonucleic Acid; C000913:cobamamide