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Journal of Bacteriology, May 2007, p. 3686-3694, Vol. 189, No. 10
0021-9193/07/$08.00+0     doi:10.1128/JB.01890-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Novel Fur- and Iron-Regulated Small RNA, NrrF, Is Required for Indirect Fur-Mediated Regulation of the sdhA and sdhC Genes in Neisseria meningitidis{triangledown} ,{dagger}

J. R. Mellin,1,2 Sulip Goswami,1 Susan Grogan,1 Brian Tjaden,3 and Caroline A. Genco1,2*

Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, Boston, Massachusetts 02118,1 Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118,2 Computer Science Department, Wellesley College, Wellesley, Massachusetts 024813

Received 14 December 2006/ Accepted 23 February 2007

Iron is both essential for bacterial growth and toxic at higher concentrations; thus, iron homeostasis is tightly regulated. In Neisseria meningitidis the majority of iron-responsive gene regulation is mediated by the ferric uptake regulator protein (Fur), a protein classically defined as a transcriptional repressor. Recently, however, microarray studies have identified a number of genes in N. meningitidis that are iron and Fur activated, demonstrating a new role for Fur as a transcriptional activator. Since Fur has been shown to indirectly activate gene transcription through the repression of small regulatory RNA molecules in other organisms, we hypothesized that a similar mechanism could account for Fur-dependent, iron-activated gene transcription in N. meningitidis. In this study, we used a bioinformatics approach to screen for the presence of Fur-regulated small RNA molecules in N. meningitidis MC58. This screen identified one small RNA, herein named NrrF (for neisserial regulatory RNA responsive to iron [Fe]), which was demonstrated to be both iron responsive and Fur regulated and which has a well-conserved orthologue in N. gonorrhoeae. In addition, this screen identified a number of other likely, novel small RNA transcripts. Lastly, we utilized a new bioinformatics approach to predict regulatory targets of the NrrF small RNA. This analysis led to the identification of the sdhA and sdhC genes, which were subsequently demonstrated to be under NrrF regulation in an nrrF mutant. This study is the first report of small RNAs in N. meningitidis and the first to use a bioinformatics approach to identify, a priori, regulatory targets of a small RNA.


* Corresponding author. Mailing address: 650 Albany St., Rm. 314, Boston, MA 02118. Phone: (617) 414-5305. Fax: (617) 638-7124. E-mail: caroline.genco{at}bmc.org or cgenco{at}bu.edu

{triangledown} Published ahead of print on 9 March 2007.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.


Journal of Bacteriology, May 2007, p. 3686-3694, Vol. 189, No. 10
0021-9193/07/$08.00+0     doi:10.1128/JB.01890-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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