Sigma factor

A sigma factor (&sigma; factor) is a prokaryotic transcription initiation factor that must be part of RNA polymerase (RNAP) for specific binding to promoter sites on DNA. Different sigma factors are activated in response to different environmental conditions, as are listed below. 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. All sigma factors are distinguished by their characteristic molecular weights. For example, &sigma;70 refers to the sigma factor with a molecular weight of 70 kDa.

Sigma Retention
The complex of core RNA polymerase (consisting of 2 alpha, 1 beta, 1 beta-prime, and 1 omega subunits) with sigma factor is a called RNA polymerase holoenzyme. It was previously believed that RNA polymerase holoenzyme initiates transcription, while RNA polymerase core enzyme carries out RNA synthesis. 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 &sigma;70 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 infinitely long at initiation (too long to be measured in a typical biochemical experiment) to a shorter lifetime upon transition to elongation (which can be addressed in a typical biochemical experiment).

Alternative sigma factors are important in producing different mRNA strands than those produced by the cell under normal conditions. The new mRNA will create proteins that in turn will help the cell to survive the new conditions.

Structure
Sigma factors have four main regions that are generally conserved:

N-C 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 &sigma;54-type sigma factors. Proteins homologous to &sigma;54/RpoN are functional sigma factors, but they have significantly different primary amino acid sequences.

Specialized Sigma Factors
Developmental responses involve transcription of genes by RNAP containing specialized sigma factors. Different sigma factors can be expressed when a cell is exposed to different conditions.

E.coli sigma factors:
 * &sigma;70 (RpoD) - the "housekeeping" sigma factor, transcribes most genes in growing cells. Makes the proteins that are necessary to keep the cell alive.
 * &sigma;54 (RpoN) - the nitrogen-limitation sigma factor
 * &sigma;38 (RpoS) - the starvation/stationary phase sigma factor
 * &sigma;32 (RpoH) - the heat shock sigma factor, it is turned on when exposed to heat
 * &sigma;28 (RpoF) - the flagellar sigma factor
 * &sigma;24 (RpoE) - the extracytoplasmic/extreme heat stress sigma factor
 * &sigma;19 (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.