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

Mol Cell. 2017 Jan 19;65(2):220-230. doi: 10.1016/j.molcel.2016.11.019. Epub 2016 Dec 15.

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.

Keywords: EmrE; SugE; aptamer; multidrug efflux; noncoding RNA; orphan riboswitch; urea carboxylase; ykkC.

MeSH terms

  • 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*
  • Gene Expression Regulation, Bacterial
  • Gene Expression Regulation, Enzymologic
  • Guanidine / metabolism*
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Nucleic Acid Conformation
  • Nucleotide Motifs
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Riboswitch*
  • Substrate Specificity

Substances

  • Bacterial Proteins
  • Membrane Transport Proteins
  • RNA, Bacterial
  • RNA, Messenger
  • Riboswitch
  • Carbon-Nitrogen Ligases
  • urea carboxylase (hydrolyzing)
  • Guanidine