Sigma 38
Encyclopedia
Sigma factors
are proteins that regulate transcription
in bacteria
. Sigma factors can be activated in response to different environmental conditions. The gene rpoS encodes sigma-38 (σ38, or RpoS), a 37.8 kD protein in Escherichia coli
. rpoS is transcribed in late exponential phase, and RpoS is the primary regulator of stationary phase genes. RpoS is a central regulator of the general stress response and operates in both a retroactive and a proactive manner: not only does it allow the cell to survive environmental challenges, but it also prepares the cell for subsequent stresses (cross-protection) (Hengge-Aronis, 2002). The rpoS gene most likely originated in the γ branch of the proteobacteria
(as reviewed in Hengge-Aronis, 2002).
, translation
, degradation, and protein activity. These processes occur in response to stresses such as near-UV radiation, acid, temperature or osmotic shock, oxidative stress, 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.
which may hinder transcriptional elongation or stability in response to amino acid limitation, or carbon, nitrogen or phosphorus starvation (Gentry et al., 1993). Despite the numerous controls on rpoS transcription, cellular rpoS mRNA levels remain high during exponential phase and the majority of extracellular stimuli do not significantly affect rpoS transcription.
s) 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 (Sledjeski et al., 1996). Another sRNA, RprA, stimulates rpoS translation in response to cell surface stress signaled via the RcsC sensor kinase (Sledjeski et al., 1996). A third type of sRNA, OxyS, is regulated by OxyR, the primary sensor of oxidative shock (Altuvia et al., 1997). 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 (Brown and Elliott, 1996). 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.
and is needed for desiccation resistance (Kaasen et al., 1992). Additional RpoS-dependent factors involved in oxidative stress include glutathione reductase (encoded by gor), and superoxide dimutase (encoded by sodC) (Beckerhapak and Eisenstark, 1995).
(ecnAB) locus which encodes a lysis-inducing toxin (Bishop et al., 1998). In contrast, ssnA is negatively controlled by RpoS but it also promotes lysis. Paradoxically, lysis is seen as a survival process in certain contexts.
Sigma factor
A sigma factor is a bacterial transcription initiation factor that enables specific binding of RNA polymerase to gene promoters. Different sigma factors are activated in response to different environmental conditions...
are proteins that regulate transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
in bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. Sigma factors can be activated in response to different environmental conditions. The gene rpoS encodes sigma-38 (σ38, or RpoS), a 37.8 kD protein in Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
. rpoS is transcribed in late exponential phase, and RpoS is the primary regulator of stationary phase genes. RpoS is a central regulator of the general stress response and operates in both a retroactive and a proactive manner: not only does it allow the cell to survive environmental challenges, but it also prepares the cell for subsequent stresses (cross-protection) (Hengge-Aronis, 2002). The rpoS gene most likely originated in the γ branch of the proteobacteria
Proteobacteria
The Proteobacteria are a major group of bacteria. They include a wide variety of pathogens, such as Escherichia, Salmonella, Vibrio, Helicobacter, and many other notable genera....
(as reviewed in Hengge-Aronis, 2002).
Environmental signal to activation: regulation of RpoS
Regulatory mechanisms that control RpoS exist at various levels of gene and protein organization: transcriptionTranscription (linguistics)
Transcription in the linguistic sense is the systematic representation of language in written form. The source can either be utterances or preexisting text in another writing system, although some linguists only consider the former as transcription.Transcription should not be confused with...
, translation
Translation
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. Whereas interpreting undoubtedly antedates writing, translation began only after the appearance of written literature; there exist partial translations of the Sumerian Epic of...
, degradation, and protein activity. These processes occur in response to stresses such as near-UV radiation, acid, temperature or osmotic shock, oxidative stress, 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 (Lange et al., 1995). rpoSp promotes transcription of rpoS mRNA, and is induced upon entry into stationary-phase in cells growing on rich media (Takayanagi et al., 1994) via an unknown mechanism. Flanking rpoSp are two putative cAMP-CRP (cyclic AMP-cAMP receptor protein) binding sites that seem to control rpoS transcription in an antagonistic manner. The position of the first site upstream of the major rpoS promoter corresponds to a “classical activator” similarly found in the lac promoter thereby suggesting that its effects on transcription are activating (Lange and Hengge-Aronis, 1994); in contrast, the location of the second cAMP-CRP site is indicative of inhibitory action. In exponential phase, crp mutants exhibit high levels of rpoS expression, suggesting that cAMP-CRP inhibits rpoS transcription. Upon entry into stationary phase, on the other hand, cAMP-CRP may upregulate rpoS transcription (Hengge-Aronis, 2002). While these observations may explain the seemingly dual nature of the cAMP-CRP binding sites, they require an explanation of phase-dependent selection of cAMP-CRP site activation to fully account for the contradictory data. Additional regulatory controls for rpoS transcription include: BarA, a histidine sensor kinase which can activate OmpR and thereby promote porin synthesis; levels of small molecules such as ppGpppGuanosine pentaphosphate
ppGpp, guanosine pentaphosphate or tetraphosphate is an alarmone which is involved in the stringent response in bacteria, causing the inhibition of RNA synthesis when there is a shortage of amino acids present. This causes translation to decrease and the amino acids present are therefore conserved...
which may hinder transcriptional elongation or stability in response to amino acid limitation, or carbon, nitrogen or phosphorus starvation (Gentry et al., 1993). Despite the numerous controls on rpoS transcription, cellular rpoS mRNA levels remain high during exponential phase and the majority of extracellular stimuli do not significantly affect rpoS transcription.
Translational control of rpoS
Most RpoS expression is determined at the translational level (Repoila et al., 2003). sRNAs (small noncoding RNARNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
s) 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 (Sledjeski et al., 1996). Another sRNA, RprA, stimulates rpoS translation in response to cell surface stress signaled via the RcsC sensor kinase (Sledjeski et al., 1996). A third type of sRNA, OxyS, is regulated by OxyR, the primary sensor of oxidative shock (Altuvia et al., 1997). The mechanism by which OxyS interferes with rpoS mRNA translational efficiency
Translational efficiency
Translational efficiency, in the context of cell biology, is the rate of mRNA translation into proteins within cells....
is not known. However, the RNA-binding protein Hfq is implicated in the process (Brown and Elliott, 1996). Hfq binds to rpoS mRNA in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
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 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 DNA damage, presence of reactive oxygen species and osmotic stress. The product of xthA is an exonuclease that participates in DNA repair by recognizing and removing 5’ monophosphates near abasic sites in damaged DNA (Demple et al., 1983). Likewise, catalases HPI and HPII, encoded by katG and katE convert harmful hydrogen peroxide molecules to water and oxygen (Loewen, 1992). The otsBA gene product trehalose functions as an osmoprotectantOsmoprotectant
Osmoprotectants or compatible solutes are small molecules that act as osmolytes and help organisms survive extreme osmotic stress. Examples include betaines, amino acids, and the sugar trehalose. These molecules accumulate in cells and balance the osmotic difference between the cell's surroundings...
and is needed for desiccation resistance (Kaasen et al., 1992). Additional RpoS-dependent factors involved in oxidative stress include glutathione reductase (encoded by gor), and superoxide dimutase (encoded by sodC) (Beckerhapak and Eisenstark, 1995).
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), 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 (Lange et al., 1995). 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 Krebs cycle activity and increased glyocolytic activity to limit the reactive oxygen species that are byproduced as a result of essential cellular processes. Pyruvate entry into the Krebs cycle is inhibited by the product of the RpoS-dependent gene poxB. An overall slowdown in metabolic activity is consistent with energy conservation and reduced growth during periods of stress.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 (reviewed in Hengge-Aronis, 2000). Discovery of RpoS-dependent virulence genes in Salmonella are 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 interestingly, required for growth in deep lymphoid tissue such as the spleen and liver (Gulig et al., 1993).Lysis
RpoS also plays an important role in regulating cell lysis. Along with OmpR, it upregulates the entericidinEntericidin
In molecular biology, entericidins are bacterial antidote/toxin peptides. The entericidin locus is activated in the stationary phase of growth under high osmolarity conditions by rho-S and simultaneously repressed by the osmoregulatory EnvZ/OmpR signal transduction pathway...
(ecnAB) locus which encodes a lysis-inducing toxin (Bishop et al., 1998). In contrast, ssnA is negatively controlled by RpoS but it also promotes lysis. Paradoxically, lysis is seen as a survival process in certain contexts.