Metabolism of Free Guanidine in Bacteria Is Regulated by a Widespread Riboswitch Class

• Published in: Molecular cell Vol. 65; no. 2; pp. 220 - 230
• Main Authors: Nelson, James W., Atilho, Ruben M., Sherlock, Madeline E., Stockbridge, Randy B., Breaker, Ronald R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.01.2017
• Subjects: aptamer; Bacteria - genetics; Bacteria - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Binding Sites; Carbon-Nitrogen Ligases - chemistry; Carbon-Nitrogen Ligases - genetics; Carbon-Nitrogen Ligases - metabolism; EmrE; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Guanidine - metabolism; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; multidrug efflux; noncoding RNA; Nucleic Acid Conformation; Nucleotide Motifs; orphan riboswitch; Riboswitch; RNA, Bacterial - chemistry; RNA, Bacterial - genetics; RNA, Bacterial - metabolism; RNA, Messenger - chemistry; RNA, Messenger - genetics; RNA, Messenger - metabolism; Substrate Specificity; SugE; urea carboxylase; ykkC; urea carboxylase; ykkC; noncoding RNA; aptamer; SugE; multidrug efflux; EmrE; orphan riboswitch
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2016.11.019

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. [Display omitted] •Bacteria naturally produce, sense, and respond to guanidine•Most ykkC RNA motif representatives are aptamer domains of guanidine riboswitches•Riboswitches control guanidine carboxylase genes previously declared urea carboxylases•Many annotated EmrE and SugE multidrug efflux pumps are likely guanidine transporters In this paper, Nelson et al. demonstrate that a widespread riboswitch class senses free guanidine and controls the expression of numerous genes involved in its detoxification and export, demonstrating the existence of a fundamental aspect of bacterial metabolism that was previously unrecognized.