Disease relevance of hfq

• Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K-12 [1].
• The region immediately downstream from the miaA tRNA modification gene at 94.8 min contains the hfq gene and the hflA region, which are important in the bacteriophage Q beta and lambda life cycles [1].
• On the other hand, both hfq insertions interfered with lambda phage plaque formation, probably by means of polarity at the hflA region [1].
• The RNA binding protein host factor I (HF-I) encoded by the hfq gene is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology [2].
• yst gene expression in Yersinia enterocolitica is positively regulated by a chromosomal region that is highly homologous to Escherichia coli host factor 1 gene (hfq) [3].

High impact information on hfq

• Using a combination of gene fusion analysis and pulse-chase experiments, we demonstrate that the hfq mutant is specifically impaired in rpoS translation [4].
• Inactivation of the hfq gene reduces the length of poly(A) tails synthesized at the 3' end of the rpsO mRNA by poly(A) polymerase I in vivo [5].
• In hfq mutant cells with a deficient Hfq gene product, the RNA-binding activity is missing, and analysis of the ompA mRNA showed that the growth-rate dependence of degradation is lost [6].
• The deduced amino acid sequence is similar to that of HF-I, an RNA-binding protein of Escherichia coli, which is required for replication of bacteriophage Q beta RNA [7].
• Analysis of mRNA half-lives in hfq, deltapcnB and hfq deltapcnB mutants suggests that Hfq and PAP I function in the same mRNA decay pathway [8].

Biological context of hfq

• Lack of Hfq also increased the amounts and stabilities of transcripts initiated from P(miaA) and P1hfqHS, two of the promoters for hfq, suggesting autoregulation, but did not change the half-life of bulk mRNA [9].
• We report here that mutations in hfq and rpoS reversed the stationary-phase down-regulation of the amounts of MutS and MutH. hfq regulation of the amount of MutS in stationary-phase cultures was mediated by RpoS-dependent and -independent mechanisms, whereas hfq regulation of the amount of MutH was mediated only through RpoS [9].
• RNA phage production was observed in Escherichia coli hfq mutant strains transformed with plasmids containing genomic cDNA of phages Qbeta or MS2 [10].
• We have mapped two Hfq binding sites in the 5'-untranslated region of hfq mRNA and show that Hfq binding inhibits formation of the translation initiation complex [11].
• Negative regulatory role of the Escherichia coli hfq gene in cell division [12].

Anatomical context of hfq

• The Brucella abortus hfq mutant, unlike its parental strain 2308, fails to replicate in cultured murine macrophages, and is rapidly cleared from the spleens and livers of experimentally infected BALB/c mice [13].
• The intracellular level of HF-I is about 30,000 to 60,000 molecules per cell, the majority being associated with ribosomes as one of the salt wash proteins [14].
• In contrast to B. abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1(+) phagosomes and failed to initiate intracellular replication [15].
• To determine the effect of antibody opsonization on the ability of Brucella to establish itself within monocytes, the intracellular trafficking of virulent Brucella abortus 2308 and attenuated hfq and bacA mutants was followed in the human monocytic cell line THP-1 [15].

Associations of hfq with chemical compounds

• We have constructed a PAO1hfq- mutant and a PAO1hfq-rpoS- double mutant to permit distinction between direct and indirect effects of Hfq.When compared to the wild-type and the rpoS- strains, the hfq knock out strain showed a reduced growth rate and was unable to utilize glucose as a sole carbon source [16].
• Transcription of hfq is induced under various stress conditions, including osmotic and ethanol stress and at the entry into the stationary growth phase, thus supporting the view that Hfq is important for the growth and survival of L. monocytogenes in harsh environments [17].

Physical interactions of hfq

• The hfq-encoded RNA-binding protein HF-I has long been known as a host factor for phage Qbeta RNA replication and has recently been shown to be essential for translation of rpoS, which encodes the sigmaS subunit of RNA polymerase [18].

Other interactions of hfq

• An omega (omega) cassette insertion near the end of hfq resulted in phenotypes only slightly different from the parent, although transcript mapping demonstrated that the insertion was completely polar on hflX expression [1].
• We report here the transcriptional pattern and possible posttranscriptional regulation of mutL, miaA and hfq genes of this superoperon [19].
• Comparison of the transcriptome of an hfq mutant with that of an rseA mutant, which also overexpresses sigma(E), revealed that sigma(E) controls approximately half the genes found to be upregulated in the hfq mutant [20].
• In this study we have performed a mutational analysis of the Escherichia coli hfq gene, and have studied the effects of amino acid substitutions at several positions in the Hfq protein as well as of C-terminal truncations on its role in phage Qbeta replication, in repression of a target mRNA, and on the stability of the small regulatory RNA DsrA [21].

Analytical, diagnostic and therapeutic context of hfq

• Assays of Beta-galactosidase in strains with rpoS-lac fusions, Western blot (immunoblot) analysis, and pulse-labeling and immunoprecipitation of both fusion proteins and native RpoS show that an S. typhimurium hfq mutant has a four- to sevenfold reduction in expression of rpoS that is attributable primarily to a defect in translation [22].
• Sequence determination of the cloned hfq gene indicated that HF-I is a small protein of Mr 11,166 consisting of 102 amino acid residues [23].

References