rpoS
This article needs additional citations for verification. (May 2011) |
The gene rpoS (RNA polymerase, sigma S, also called katF) encodes the
Environmental signal to activation: regulation of RpoS
Regulatory mechanisms that control RpoS exist at various levels of gene and protein organization:
, and nutrient deprivation. While many key regulatory entities have been identified in these areas, the precise mechanisms by which they signal rpoS transcription, translation, proteolysis or activity remain largely uncharacterized.Transcriptional control of rpoS
Transcription of rpoS in E. coli is mainly regulated by the chromosomal rpoSp promoter.
Translational control of rpoS
Most RpoS expression is determined at the translational level.[6] sRNAs (small noncoding RNAs) sense environmental changes and in turn increase rpoS mRNA translation to allow the cell to accordingly adjust to external stress. The promoter of the 85 nucleotide sRNA DsrA contains a temperature-sensitive transcription initiation thermocontrol as it is repressed at high (42˚C) temperatures, but induces (perhaps by complementary binding to) rpoS at low (25˚C) temperatures.[7] Another sRNA, RprA, stimulates rpoS translation in response to cell surface stress signaled via the RcsC sensor kinase.[7] A third type of sRNA, OxyS, is regulated by OxyR, the primary sensor of oxidative shock.[8] The mechanism by which OxyS interferes with rpoS mRNA translational efficiency is not known. However, the RNA-binding protein Hfq is implicated in the process.[9] Hfq binds to rpoS mRNA in vitro and may thereby modify rpoS mRNA structure for optimal translation. Hfq activates both DsrA and RprA. In contrast, LeuO inhibits rpoS translation by repressing dsrA expression and the histone-like protein HN-S (and its paralog StpA) inhibits rpoS translation via an unknown mechanism. In addition, H-NS, LeuO, Hfq and DsrA form an interconnected regulatory network that ultimately controls rpoS translation.
RpoS translation was also shown to be controlled in other bacterial species, beside Escherichia coli. E.g., in the opportunistic human pathogen Pseudomonas aeruginosa the sRNA ReaL translationally silences rpoS mRNA.[10]
RpoS degradation
RpoS proteolysis forms another level of the sigma factor’s regulation. Degradation occurs via ClpXP, a barrel-shaped protease composed of two six-subunit rings of the ATP-dependent ClpX chaperone that surround two seven-subunit rings of ClpP (Repoila et al., 2003). The response regulator RssB has been identified as a σS-specific recognition factor crucial for RpoS degradation. Additional factors known to regulate RpoS proteolysis but via incompletely characterized mechanisms include: RssA which is found on the same operon as RssB; H-NS and DnaK, both of which also regulate rpoS mRNA translation, and LrhA; and acetyl phosphate affects RpoS proteolysis by possibly acting as a phosphoryl donor to RssB.
The RpoS regulon
Consistent with its role as the master controller of the bacterial stress response, RpoS regulates the expression of stress-response genes that fall into various functional categories: stress resistance, cell morphology, metabolism, virulence and lysis.
Stress resistance
Many genes under RpoS control confer stress resistance to assaults such as
It has also been found, using comparative proteomic analysis with B. pseudomallei, that rpoS regulates eight oxidative responsive proteins including ScoA (a SCOT subunit) not previously known for oxidative stress response involvement. The regulatory effect in this case is RpoS down regulation of SCOT expression in response to oxidative stress in B. pseudomallei. [15]
Morphology
RpoS-dependent genes involved in changes in cell membrane permeability and general cell morphology mostly belong to the osm family of genes. osmB encodes an outer membrane lipoprotein that may play a role in cell aggregation (Jung et al., 1990) ,[15] whereas osmY encodes a periplasmic protein. Additional RpoS-dependent factors that determine the size and shape of the cell include the morphogene bolA and products of the ftsQAZ operon that play a role in the timing of cell division.[4] Control of cell shape, cell division and cell-cell interaction are likely to be important in inhibiting cell proliferation and thus allocating resources to cell survival during periods of stress.
Metabolism
Metabolically-optimal survival conditions include RpoS-dependent decreased
Virulence
As a defense mechanism, the host environment is hostile to invading pathogens. Therefore, infection can be a stressful event for pathogenic bacteria and control of virulence genes may be temporally correlated with the timing of infection by pathogens.[16] Discovery of RpoS-dependent virulence genes in Salmonella is consistent with RpoS as a general regulator of the stress response: the spv gene found on a virulence plasmid in this bacterium is controlled by RpoS and is required for growth in deep lymphoid tissue such as the spleen and liver.[17]
Lysis
RpoS also plays an important role in regulating cell lysis. Along with OmpR, it upregulates the entericidin (ecnAB) locus which encodes a lysis-inducing toxin.[18] In contrast, ssnA is negatively controlled by RpoS but it also promotes lysis. Paradoxically, lysis is seen as a survival process in certain contexts.
References
Further reading
- Demple B, Halbreok J, Linn S (1983). "Escherichia coil xth mutants are hypersensitive to hydrogen peroxide". J. Bacteriol. 153 (2): 1079–1082. PMID 6337115.
- Hengge-Aronis R, Klein W, Lange R, Rimmele M, Boos W (December 1991). "Trehalose synthesis genes are controlled by the putative sigma factor encoded by rpoS and are involved in stationary-phase thermotolerance in Escherichia coli". Journal of Bacteriology. 173 (24): 7918–24. PMID 1744047.