Sigma factor: Difference between revisions

The '''σ-factor''' performs two chief functions: to direct the catalytic core of RNAP to the  promotoer upstream of the +1 start site of transcription, and finally to assist in the initiation of strand seperation of double-helical DNA, forming the transcription "bubble."[1] Each gene promoter utilizes a specific promoter region about 40 bp upstream of the transcription start site,  and therefore different σ-factors play a role in the regulation of different genes [2].  This process, which includes association of the σ-factor with RNAP to recognize and open DNA at the promoter site, followed by dissociation of the σ to allow elongation, which can then activate additional RNAP enzymes, is referred to as the '''σ-cycle''' [3].

There are many types of σ-subunits, and each recognizes a unique promoter sequence.  Furthmore, each unique σ is composed of a variable number of structured domains.  The simplest σ-factors have two domains, few have three, and most, called '''housekeeping σ-factors''', have 4 domains, given the names σ(4), σ(3), σ(2), and σ(1.1) [1,3].  All domains are linked by very flexible peptide '''linkers''' which can extend very long  distances.  Each of these domains utilizes DNA-binding determinants, or domains that recognize specific sequences and conformations in DNA.  Most commonly, these recognized sequences occur at the -35 and -10 locations upstream of the +1 site.  One such DNA-binding motif, '''the helix-turn-helix motif''' (<scene name='59/591940/Hth_motif/2'>HTH</scene>), helps specifically recognize DNA promoters at both the -35 and -10 positions [1].  This HTH motif, used by most σ-factors, maintains its specificity and accuracy by binding in the '''major groove''' of DNA, where it can interact with the base pairs in the DNA double-helix.  In many prokaryotes, these portions of DNA maintain consensus adenosine and thymine sequences [1,2], such as <scene name='59/591940/Ta_sequence/1'>TATAAT</scene>.   

The <scene name='59/591940/Transcription_bubble/1'>transcription bubble</scene>, also referred to as the '''open complex''' is formed through the common '''housekeeping σ factors''' which unwind about 13 bp of duplex DNA in an ATP independent process.  Research has shown that σ factors require invariant basic and aromatic residues (Phe, Tyr, Trp) critical for this formation [1].  The process of bubble formation begins at the -11 formation (usually A) and propogates to +1 site, through a phenomenon called <scene name='59/591940/Transcription_bubble_flipped/1'>Base Flipping</scene>, which interrupts the stacking interactions stabilizing the double helix conformation [1].  As this process occurs and the DNA transitions into the open promoter complex, certain RNAP-σ contacts are lost, initiating the dissociation of σ.  In summary, the processes of -35 and -10 motif sequence recognition and helix strand separation are coupled by the σ factor.   

Initiation of prokaryotic transcription requires cooperation between the σ peptide and RNAP.  Without these fundamental interactions, no transcription is possible.

Normally, σ-factor domains cannot bind to promoters on their own.  These domains usually are placed in very compacted positions relative to each other, a conformation that buries DNA-binding determinants.  This type of restriction is called '''conformational restriction'''[1].  Additionally, in housekeeping σs, a domain called the '''σ(1.1)''' stabilizes the compact conformation mentioned above, thereby preventing any promoter recognition.  This method of restricting the binding abilities of isolated σ's is called '''autoinhibitory inhibition'''[1].   

(4), which allows them to make energy-favorable interactions with RNAP residues. This causes a cascading "peeling off" effect of other σ-domains from the RNAP, preventing any interaction with duplex DNA and inhibiting transcription in an analogous process to competitive inhibition [3].

Since σ-factors are exclusively linked to gene expression in prokaryotic organisms, the variety of σ-factors in a cell dictate how and what genes are transcribed.  Specialized function in cells, therefore, is highly moderated by its arsenal of σ-subunits.  In fact, cellular development and differentiation are directly impacted and carried out by "cascades" of σ-factors. In the early stages of development, '''early genes'''[2] are transcribed by basic '''bacterial σ-factors'''.  These genes are therefore transcribed to give new σ-factors, which in turn activate additional genes, and so on [2].  This process of σ-factor cascades demonstrates the versatile and essential biologic functions of the RNAP subunit, σ.  

1.  Felklistov, Andrey, Brian D. Sharon, Seth A. Darst, and Carol A. Gross. "Bacterial Sigma Factors: A Historical, Structural, and Genomic Perspective." The Annual Review of Microbiology 68 (2014): 357-76.  

2.  Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. 3rd ed. Hoboken, NJ: Wiley, 2008.

3.  Mooney, R. A., S. A. Darst, and R. Landick. "Sigma and RNA Polymerase: An On-again, Off-again Relationship?" Molecular Cell 20.3 (2005): 335-45.