Sigma factor
Encyclopedia
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. Every molecule of RNA polymerase
contains exactly one sigma factor subunit, which in the model bacterium Escherichia coli
is one of those listed below. E. coli has seven sigma factors; the number of sigma factors varies between bacterial species. Sigma factors are distinguished by their characteristic molecular weights. For example, σ70 refers to the sigma factor with a molecular weight of 70 kDa.
N-terminus --------------------- C-terminus
1.1 2 3 4
The regions are further subdivided (e.g. 2 includes 2.1, 2.2, etc.)
The exception to this organization is in σ54-type sigma factors. Proteins homologous to σ54/RpoN are functional sigma factors, but they have significantly different primary amino acid sequences.
Sigma factors in E. coli
:
There are also anti-sigma factors
that inhibit the function of sigma factors and anti-anti-sigma factors that restore sigma factor function.
holoenzyme. It was previously believed that the RNA polymerase holoenzyme initiates transcription, while the core RNA polymerase alone synthesizes RNA. Thus, the accepted view was that sigma factor must dissociate upon transition from transcription initiation to transcription elongation (this transition is called "promoter escape"). This view was based on analysis of purified complexes of RNA polymerase stalled at initiation and at elongation. Finally, structural models of RNA polymerase complexes predict that as the growing RNA product becomes longer than ~10 nucleotides sigma must be "pushed out" of the holoenzyme, since there is a steric clash between RNA and a sigma domain. However, a recent study (reference*2) has shown that σ70 remains attached in complex with the core RNA polymerase, at least during early elongation. Indeed, the phenomenon of promoter-proximal stalling suggests that sigma may play a role during early elongation. All studies are consistent with the assumption that promoter escape reduces the lifetime of the sigma-core interaction from very long at initiation (too long to be measured in a typical biochemical experiment) to a shorter, measurable lifetime upon transition to elongation.
However, Elbright and coworkers, using the FRET technique later proposed that the σ does not leave the core. Instead, the σ changes its binding with the core during initiation and elongation. Therefore, the σ cycles between a tightly bound state during initiation to a strongly bound state during elongation.
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...
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...
initiation factor that enables specific binding of RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
to gene promoters. Different sigma factors are activated in response to different environmental conditions. Every molecule of RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
contains exactly one sigma factor subunit, which in the model bacterium 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...
is one of those listed below. E. coli has seven sigma factors; the number of sigma factors varies between bacterial species. Sigma factors are distinguished by their characteristic molecular weights. For example, σ70 refers to the sigma factor with a molecular weight of 70 kDa.
Structure
Sigma factors have four main regions that are generally conserved:N-terminus --------------------- C-terminus
1.1 2 3 4
The regions are further subdivided (e.g. 2 includes 2.1, 2.2, etc.)
- Region 1.1 is found only in "primary sigma factors" (RpoD, RpoS in E.coli). It is involved in ensuring the sigma factor will only bind the promoter when it is complexed with the RNA polymerase.
- Region 2.4 recognizes and binds to the Pribnow boxPribnow boxThe Pribnow box is the sequence TATAAT of six nucleotides that is an essential part of a promoter site on DNA for transcription to occur in bacteria...
. - Region 4.2 recognizes and binds to the -35 promoter site.
The exception to this organization is in σ54-type sigma factors. Proteins homologous to σ54/RpoN are functional sigma factors, but they have significantly different primary amino acid sequences.
Specialized sigma factors
Different sigma factors are activated under different environmental conditions. These specialized sigma factors bind the promoters of genes appropriate to the environmental conditions, increasing the transcription of those genes.Sigma factors in E. 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...
:
- σ70 (RpoD) - the "housekeeping" sigma factor or also called as primary sigma factor, transcribes most genes in growing cells. Makes the proteins necessary to keep the cell alive.
- σ54 (RpoN) - the nitrogen-limitation sigma factor
- σ38Sigma 38Sigma 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 , a 37.8 kD protein in Escherichia coli. rpoS is transcribed in late exponential phase, and RpoS is the primary...
(RpoS) - the starvation/stationary phase sigma factor - σ32 (RpoH) - the heat shock sigma factor, it is turned on when exposed to heat
- σ28 (RpoF) - the flagellar sigma factor
- σ24 (RpoE) - the extracytoplasmic/extreme heat stress sigma factor
- σ19 (FecI) - the ferric citrate sigma factor, regulates the fec gene for iron transport
There are also anti-sigma factors
Anti-sigma factors
In the regulation of gene expression in prokaryotes, anti-sigma factors bind to RNA polymerases and inhibit transcriptional activity. Anti-sigma factors have been found in Escherichia coli, Salmonella, and T4 bacteriophage...
that inhibit the function of sigma factors and anti-anti-sigma factors that restore sigma factor function.
Retention during transcription elongation
The core RNA polymerase (consisting of 2 alpha (α), 1 beta (β), 1 beta-prime (β'), and 1 omega (ω) subunits) binds a sigma factor to form a complex called the RNA polymeraseRNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
holoenzyme. It was previously believed that the RNA polymerase holoenzyme initiates transcription, while the core RNA polymerase alone synthesizes RNA. Thus, the accepted view was that sigma factor must dissociate upon transition from transcription initiation to transcription elongation (this transition is called "promoter escape"). This view was based on analysis of purified complexes of RNA polymerase stalled at initiation and at elongation. Finally, structural models of RNA polymerase complexes predict that as the growing RNA product becomes longer than ~10 nucleotides sigma must be "pushed out" of the holoenzyme, since there is a steric clash between RNA and a sigma domain. However, a recent study (reference*2) has shown that σ70 remains attached in complex with the core RNA polymerase, at least during early elongation. Indeed, the phenomenon of promoter-proximal stalling suggests that sigma may play a role during early elongation. All studies are consistent with the assumption that promoter escape reduces the lifetime of the sigma-core interaction from very long at initiation (too long to be measured in a typical biochemical experiment) to a shorter, measurable lifetime upon transition to elongation.
σ Cycle
According to Travers and Burgess, the σ factor leaves the core enzyme once it has initiated transcription, and the free σ can link to another core enzyme, to initiate transcription at another site. Thus, the σ cycles from one core to another.However, Elbright and coworkers, using the FRET technique later proposed that the σ does not leave the core. Instead, the σ changes its binding with the core during initiation and elongation. Therefore, the σ cycles between a tightly bound state during initiation to a strongly bound state during elongation.