title: Role of Hfq in iron-dependent and -independent gene regulation in Neisseria meningitidis.
abstract: In Neisseria meningitidis, iron-responsive gene regulation is mediated primarily by the ferric uptake regulator (Fur) protein. When complexed with iron, Fur represses gene expression by preventing transcription initiation. Fur can also indirectly activate gene expression via the repression of regulatory small RNAs (sRNA). One such Fur- and iron-regulated sRNA, NrrF, was previously identified in N. meningitidis and shown to repress expression of the sdhA and sdhC genes encoding subunits of the succinate dehydrogenase complex. In the majority of Gram-negative bacteria, sRNA-mediated regulation requires a cofactor RNA-binding protein (Hfq) for proper gene regulation and stabilization. In this study, we examined the role of Hfq in NrrF-mediated regulation of the succinate dehydrogenase genes in N. meningitidis and the effect of an hfq mutation on iron-responsive gene regulation more broadly. We first demonstrated that the stability of NrrF, as well as the regulation of sdhC and sdhA in vivo, was unaltered in the hfq mutant. Secondly, we established that iron-responsive gene regulation of the Fur-regulated sodB gene was dependent on Hfq. Finally, we demonstrated that in N. meningitidis, Hfq functions in a global manner to control expression of many ORFs and intergenic regions via iron-independent mechanisms. Collectively these studies demonstrate that in N. meningitidis, iron- and NrrF-mediated regulation of sdhC and sdhA can occur independently of Hfq, although Hfq functions more globally to control regulation of other N. meningitidis genes primarily by iron-independent mechanisms.
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Mellin
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: McClure
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Delia
authors.initials: D
authors.lastname: Lopez
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Green
authors.affiliation: Department of Chemistry and The Photonics Center, Boston University, Boston, MA 02215, USA.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Reinhard
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.|Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Genco
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D021901:DNA, Intergenic / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D035001:Host Factor 1 Protein / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D012329:RNA, Bacterial / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D021901:DNA, Intergenic; D035001:Host Factor 1 Protein; D012329:RNA, Bacterial; D007501:Iron; C087504:SodB protein, Bacteria; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase