title: Metabolism of Free Guanidine in Bacteria Is Regulated by a Widespread Riboswitch Class.
abstract: The guanidyl moiety is a component of fundamental metabolites, including the amino acid arginine, the energy carrier creatine, and the nucleobase guanine. Curiously, reports regarding the importance of free guanidine in biology are sparse, and no biological receptors that specifically recognize this compound have been previously identified. We report that many members of the ykkC motif RNA, the longest unresolved riboswitch candidate, naturally sense and respond to guanidine. This RNA is found throughout much of the bacterial domain of life, where it commonly controls the expression of proteins annotated as urea carboxylases and multidrug efflux pumps. Our analyses reveal that these proteins likely function as guanidine carboxylases and guanidine transporters, respectively. Furthermore, we demonstrate that bacteria are capable of endogenously producing guanidine. These and related findings demonstrate that free guanidine is a biologically relevant compound, and several gene families that can alleviate guanidine toxicity exist.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Nelson
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Atilho
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Madeline E
authors.initials: ME
authors.lastname: Sherlock
authors.affiliation: Department of Biophysics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Randy B
authors.initials: RB
authors.lastname: Stockbridge
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA. Electronic address: ronald.breaker@yale.edu.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Breaker
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D019791:Guanidine / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058928:Riboswitch; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D058928:Riboswitch; D019731:Carbon-Nitrogen Ligases; C023270:urea carboxylase (hydrolyzing); D019791:Guanidine
keywords: EmrE; SugE; aptamer; multidrug efflux; noncoding RNA; orphan riboswitch; urea carboxylase; ykkC