Sigma factor

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A sigma factor (σ factor) is a prokaryotic 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 at least eight 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.

[edit] Structure

Sigma factors have four main regions that are generally conserved:

N-terminus --------------------- C-terminus
             1    2    3    4

The regions are further subdivided (e.g. 2 includes 2.1, 2.2, etc.)

• Region 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 -10 promoter site.
• 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.

[edit] 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:

• σ⁷⁰ (RpoD) - the "housekeeping" sigma factor, transcribes most genes in growing cells. Makes the proteins necessary to keep the cell alive.
• σ⁵⁴ (RpoN) - the nitrogen-limitation sigma factor
• σ³⁸ (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 that inhibit the function of sigma factors.

[edit] 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 polymerase 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.

[edit] References

• Gruber TM, Gross CA. (2003). Multiple sigma subunits and the partitioning of bacterial transcription space. Annu Rev Microbiol. 57, 441-66. PMID 14527287 PDF

• Kapanidis AN, Margeat E, Laurence TA, et al (2005). "Retention of transcription initiation factor sigma70 in transcription elongation: single-molecule analysis". Mol. Cell 20 (3): 347-56. doi:10.1016/j.molcel.2005.10.012. PMID 16285917. 

[edit] External links

• MeSH Sigma+Factor