HrrF is the Fur-regulated small RNA in nontypeable Haemophilus influenzae

Estevan A. Santana, Alistair Harrison, Xinjun Zhang, Beth D. Baker, Benjamin J. Kelly, Peter White, Yunlong Liu, Robert S. Munson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Nontypeable Haemophilus influenzae (NTHi) are Gram-negative commensal bacteria that reside in the nasopharynx. NTHi can also cause multiple upper and lower respiratory tract diseases that include sinusitis, conjunctivitis, bronchitis, and otitis media. In numerous bacterial species the ferric uptake regulator (Fur) acts as a global regulator of iron homeostasis by negatively regulating the expression of iron uptake systems. However in NTHi strain 86-028NP and numerous other bacterial species there are multiple instances where Fur positively affects gene expression. It is known that many instances of positive regulation by Fur occur indirectly through a small RNA intermediate. However, no examples of small RNAs have been described in NTHi. Therefore we used RNA-Seq analysis to analyze the transcriptome of NTHi strain 86-028NPrpsL and an isogenic 86-028NPrpsLΔfur strain to identify Fur-regulated intergenic transcripts. From this analysis we identified HrrF, the first small RNA described in any Haemophilus species. Orthologues of this small RNA exist only among other Pasteurellaceae. Our analysis showed that HrrF is maximally expressed when iron levels are low. Additionally, Fur was shown to bind upstream of the hrrF promoter. RNA-Seq analysis was used to identify targets of HrrF which include genes whose products are involved in molybdate uptake, deoxyribonucleotide synthesis, and amino acid biosynthesis. The stability of HrrF is not dependent on the RNA chaperone Hfq. This study is the first step in an effort to investigate the role small RNAs play in altering gene expression in response to iron limitation in NTHi.

Original languageEnglish (US)
Article numbere105644
JournalPLoS One
Volume9
Issue number8
DOIs
StatePublished - Aug 26 2014

Fingerprint

Haemophilus influenzae
RNA
uptake mechanisms
Iron
iron
Gene expression
Pasteurellaceae
Haemophilus
Deoxyribonucleotides
sinusitis
nasopharynx
Respiratory Tract Diseases
Gene Expression
bronchitis
otitis media
molybdates
gene expression
Pulmonary diseases
conjunctivitis
Conjunctivitis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Santana, E. A., Harrison, A., Zhang, X., Baker, B. D., Kelly, B. J., White, P., ... Munson, R. S. (2014). HrrF is the Fur-regulated small RNA in nontypeable Haemophilus influenzae. PLoS One, 9(8), [e105644]. https://doi.org/10.1371/journal.pone.0105644

HrrF is the Fur-regulated small RNA in nontypeable Haemophilus influenzae. / Santana, Estevan A.; Harrison, Alistair; Zhang, Xinjun; Baker, Beth D.; Kelly, Benjamin J.; White, Peter; Liu, Yunlong; Munson, Robert S.

In: PLoS One, Vol. 9, No. 8, e105644, 26.08.2014.

Research output: Contribution to journalArticle

Santana, EA, Harrison, A, Zhang, X, Baker, BD, Kelly, BJ, White, P, Liu, Y & Munson, RS 2014, 'HrrF is the Fur-regulated small RNA in nontypeable Haemophilus influenzae', PLoS One, vol. 9, no. 8, e105644. https://doi.org/10.1371/journal.pone.0105644
Santana EA, Harrison A, Zhang X, Baker BD, Kelly BJ, White P et al. HrrF is the Fur-regulated small RNA in nontypeable Haemophilus influenzae. PLoS One. 2014 Aug 26;9(8). e105644. https://doi.org/10.1371/journal.pone.0105644
Santana, Estevan A. ; Harrison, Alistair ; Zhang, Xinjun ; Baker, Beth D. ; Kelly, Benjamin J. ; White, Peter ; Liu, Yunlong ; Munson, Robert S. / HrrF is the Fur-regulated small RNA in nontypeable Haemophilus influenzae. In: PLoS One. 2014 ; Vol. 9, No. 8.
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