title: A cluster of four homologous small RNAs modulates C1 metabolism and the pyruvate dehydrogenase complex in Rhodobacter sphaeroides under various stress conditions.
abstract: In bacteria, regulatory RNAs play an important role in the regulation and balancing of many cellular processes and stress responses. Among these regulatory RNAs, trans-encoded small RNAs (sRNAs) are of particular interest since one sRNA can lead to the regulation of multiple target mRNAs. In the purple bacterium Rhodobacter sphaeroides, several sRNAs are induced by oxidative stress. In this study, we focused on the functional characterization of four homologous sRNAs that are cotranscribed with the gene for the conserved hypothetical protein RSP_6037, a genetic arrangement described for only a few sRNAs until now. Each of the four sRNAs is characterized by two stem-loops that carry CCUCCUCCC motifs in their loops. They are induced under oxidative stress, as well as by various other stress conditions, and were therefore renamed here sRNAs CcsR1 to CcsR4 (CcsR1-4) for conserved CCUCCUCCC motif stress-induced RNAs 1 to 4. Increased CcsR1-4 expression decreases the expression of genes involved in C1 metabolism or encoding components of the pyruvate dehydrogenase complex either directly by binding to their target mRNAs or indirectly. One of the CcsR1-4 target mRNAs encodes the transcriptional regulator FlhR, an activator of glutathione-dependent methanol/formaldehyde metabolism. Downregulation of this glutathione-dependent pathway increases the pool of glutathione, which helps to counteract oxidative stress. The FlhR-dependent downregulation of the pyruvate dehydrogenase complex reduces a primary target of reactive oxygen species and reduces aerobic electron transport, a main source of reactive oxygen species. Our findings reveal a previously unknown strategy used by bacteria to counteract oxidative stress.
  
  
  OBJECTIVE
  Phototrophic organisms have to cope with photo-oxidative stress due to the function of chlorophylls as photosensitizers for the formation of singlet oxygen. Our study assigns an important role in photo-oxidative stress resistance to a cluster of four homologous sRNAs in the anoxygenic phototrophic bacterium Rhodobacter sphaeroides. We reveal a function of these regulatory RNAs in the fine-tuning of C1 metabolism. A model that relates oxidative stress defense to C1 metabolism is presented.
authors.affiliation: Institut für Mikrobiologie und Molekularbiologie, Interdisziplinäres Forschungszentrum, Justus-Liebig-Universität Giessen, Giessen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Billenkamp
authors.affiliation: Institut für Mikrobiologie und Molekularbiologie, Interdisziplinäres Forschungszentrum, Justus-Liebig-Universität Giessen, Giessen, Germany.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.affiliation: Institut für Mikrobiologie und Molekularbiologie, Interdisziplinäres Forschungszentrum, Justus-Liebig-Universität Giessen, Giessen, Germany.
authors.forename: Bork A
authors.initials: BA
authors.lastname: Berghoff
authors.affiliation: Institut für Mikrobiologie und Molekularbiologie, Interdisziplinäres Forschungszentrum, Justus-Liebig-Universität Giessen, Giessen, Germany Gabriele.Klug@mikro.bio.uni-giessen.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Klug
mesh_terms: D001483:Base Sequence; D002244:Carbon / Q000378:metabolism*; D004579:Electron Transport; D015964:Gene Expression Regulation, Bacterial; D005978:Glutathione / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D018384:Oxidative Stress; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D058727:RNA, Small Untranslated / Q000235:genetics* / Q000378:metabolism*; D012242:Rhodobacter sphaeroides / Q000235:genetics* / Q000378:metabolism*; D017385:Sequence Homology
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D058727:RNA, Small Untranslated; D002244:Carbon; D005978:Glutathione