Competition for Sigma Factors Can Regulate Initiation

KEY CONCEPTS
- E. coli has seven sigma factors, each of which causes RNA polymerase to initiate at a set of promoters defined by specific −35 and −10 sequences.
- The activities of the different sigma factors are regulated by different mechanisms.
In the next few sections, we provide a few examples of regulation of initiation, elongation, and termination. Other examples will be presented in the chapters titled The Operon and Phage Strategies.
The division of labor between a core enzyme responsible for chain elongation and a sigma factor responsible for promoter selection raised the question of whether there would be more than one type of sigma factor, each specific for a different set of promoters. FIGURE 1shows the principle of a system in which a substitution of the sigma factor changes the choice of promoter.

FIGURE 1.  The sigma factor associated with core enzyme determines the set of promoters at which transcription is initiated.
E. coli often uses alternative sigma factors to respond to changes in environmental or nutritional conditions; they are listed in TABLE 1 (sigma factors are named by the molecular weight of the product or by the function of the genes they transcribe). The most abundant sigma factor, responsible for transcription of most genes under normal conditions, is σ⁷⁰ (called σ^A in most bacterial species) and is encoded by the rpoD gene. The alternative sigma factor σ^S(σ³² ) is used for making many stress-related products; σ^H (σ³² ) and σ^E (σ²⁴ ) are required for making products needed for responding to conditions that unfold proteins in the cytoplasm and periplasm, respectively; σ^N (σ⁵⁴ ) makes products needed primarily for nitrogen assimilation; σ^Fecl (σ¹⁹ ) makes a few products needed for iron transport; and σ^F (σ²⁸ ) expresses products needed for synthesis of flagella.

TABLE 17.2 In addition to σ⁷⁰ , E. coli has several sigma factors that are induced by particular environmental conditions. (A number in the name of a factor indicates its mass.)

The unfolded protein response is one of the most conserved regulatory responses in all of biology. Originally discovered as a response to an increase in temperature (and therefore called the heat-shock response), a similar set of proteins is synthesized in all three biological kingdoms that protect cells against environmental stress. Many of these heat-shock proteins are chaperones that reduce the levels of unfolded proteins by refolding them or degrading them. In E. coli, the induction of heat-shock proteins occurs at the transcription level. The gene rpoH is a regulator needed to switch on the heat-shock response. Its product, σ³² , is an alternative sigma factor that recognizes the promoters of the heat-shock genes.
The heat-shock response (mostly chaperones and proteases) is feedback regulated. The key to the control of σ³² is that the availability of these cytoplasmic proteases and chaperones is dependent on whether they are titrated away by unfolded proteins. Thus, when unfolded protein levels go down (either because the heat-shock proteins refold or degrade them or because the temperature is lowered), they no longer titrate away the proteases that degrade σ³² , and σ³² levels return to normal. Because σ⁷⁰ and σ³² compete for available core enzyme, transcription from heatshock gene promoters returns to basal levels as σ²⁴ and σ³² levels go back to normal. Thus, the set of gene products made during heat shock depends on the balance between σ⁷⁰ and σ³² . Consistent with the importance of sigma competition, the concentration of σ⁷⁰ is greater than that of core RNA polymerase under σ³² noninducing conditions.
σ³² is not the only sigma factor that controls the unfolded protein response. σ^E is induced by accumulation of unfolded proteins in the periplasmic space and outer membrane (rather than in the cytoplasm). As with σ³² , proteolysis is the key to induction of transcription of σ^E -dependent promoters. The intricate circuit responsible for regulation of σ activity is summarized in FIGURE 2. σ^E binds to a protein (RseA) that is located in the inner membrane. RseA is an example of an antisigma factor. When bound to σ^E , RseA prevents σ^E from binding to core RNA polymerase and activating σ^E promoters. These promoters transcribe products needed for refolding denatured periplasmic proteins or degrading them. Thus, the periplasmic heat-shock response is a transient feedback response controlled by the concentrations of its own gene products. The σ^E regulon responds to the levels of unfolded and denatured periplasmic proteins rather than unfolded and denatured cytoplasmic proteins.

FIGURE 2 RseA is synthesized as a protein in the inner membrane. Its cytoplasmic domain binds the σ^E factor. RseA is cleaved sequentially in the periplasmic space and then in the cytoplasm. The cytoplasmic cleavage releases σ^E .
How does RseA know when to release σ^E ? The mechanism involves regulated, sequential proteolysis of RseA. The accumulation of unfolded proteins activates a protease (DegS) in the periplasmic space, which cleaves off the C-terminal end of the RseA protein. This cleavage activates another protease, RseP, this time on the cytoplasmic face of the inner membrane. RseP cleaves the N-terminal region of RseA, ultimately releasing σ^E . σ^E can then bind core RNA polymerase and activate transcription. Thus, accumulation of unfolded proteins at the periphery of the bacterium activates the set of genes controlled by the sigma factor.

مواضيع ذات صلة

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How Does RNA Interference Work

MicroRNAs Are Widespread Regulators in Eukaryotes

Bacteria Contain Regulator RNAs

Introduction to Regulatory RNA

Noncoding RNAs Can Be Used to Regulate Gene Expression

A Riboswitch Can Alter Its Structure According to Its Environment

Introduction to Noncoding RNA

Prions Cause Diseases in Mammals

Oppositely Imprinted Genes Can Be Controlled by a Single Center

DNA Methylation Is Responsible for Imprinting

Chromosome Condensation Is Caused by Condensins