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A mixed incoherent feed-forward loop contributes to the regulation of bacterial photosynthesis genes.

Mank NN, Berghoff BA, Klug G - RNA Biol (2013)

Bottom Line: Living cells use a variety of regulatory network motifs for accurate gene expression in response to changes in their environment or during differentiation processes.In Rhodobacter sphaeroides, a complex regulatory network controls expression of photosynthesis genes to guarantee optimal energy supply on one hand and to avoid photooxidative stress on the other hand.This point-of-view provides a comparison to other described feed-forward loops and discusses the physiological relevance of PcrZ in more detail.

View Article: PubMed Central - PubMed

Affiliation: Institut für Mikrobiologie und Molekularbiologie; Universität Giessen; Giessen, Germany.

ABSTRACT
Living cells use a variety of regulatory network motifs for accurate gene expression in response to changes in their environment or during differentiation processes. In Rhodobacter sphaeroides, a complex regulatory network controls expression of photosynthesis genes to guarantee optimal energy supply on one hand and to avoid photooxidative stress on the other hand. Recently, we identified a mixed incoherent feed-forward loop comprising the transcription factor PrrA, the sRNA PcrZ and photosynthesis target genes as part of this regulatory network. This point-of-view provides a comparison to other described feed-forward loops and discusses the physiological relevance of PcrZ in more detail.

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Figure 2. (A and C) Structure and regulatory output of incoherent and coherent FFL motifs. Four different types (I1-I4 and C1-C4) are depicted, where X and Y refer to transcription factors (black boxes) and small RNAs (gray boxes), respectively. Z reflects target genes of X and Y, modified from Mangan and Alon.9 In the case of the RNAIII FFL, Rot stands on one hand for the rot mRNA, repressed by RNAIII, on the other hand for the Rot protein, repressing hla. (B) Schematic picture of the PrrA/PcrZ, RpoE/RybB and PhoP/AmgR mixed incoherent FFLs in R. sphaeroides, E. coli and S. enterica, respectively. (D) Schematic picture of mixed coherent FFLs. The OmpR-based and RNAIII-based FFLs from E. coli and S. aureus, respectively, are depicted.
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Figure 2: Figure 2. (A and C) Structure and regulatory output of incoherent and coherent FFL motifs. Four different types (I1-I4 and C1-C4) are depicted, where X and Y refer to transcription factors (black boxes) and small RNAs (gray boxes), respectively. Z reflects target genes of X and Y, modified from Mangan and Alon.9 In the case of the RNAIII FFL, Rot stands on one hand for the rot mRNA, repressed by RNAIII, on the other hand for the Rot protein, repressing hla. (B) Schematic picture of the PrrA/PcrZ, RpoE/RybB and PhoP/AmgR mixed incoherent FFLs in R. sphaeroides, E. coli and S. enterica, respectively. (D) Schematic picture of mixed coherent FFLs. The OmpR-based and RNAIII-based FFLs from E. coli and S. aureus, respectively, are depicted.

Mentions: Regulatory networks control accurate gene expression and are therefore essential to fully adapt to various stimuli like stresses or nutrient changes. One of these networks is the so-called FFL, which consists of a transcription factor X regulating a second transcription factor Y. Both protein factors jointly regulate the transcription rate of a target gene Z (Fig. 2). Whenever one of the protein factors (X or Y) is replaced by an sRNA, a post-transcriptional regulation level is inserted into the FFL. In this case it is called a mixed FFL.9 In Escherichia coli and Saccharomyces cerevisiae, one of the most common network motifs is the incoherent FFL. There are four described types of this network motif, which have in common that direct (X to Z) and indirect (X over Y to Z) regulation paths are opposite (Fig. 2A). This type of gene regulation allows for speeding up inhibition of target gene activation, which is called pulse expression.9,10 This enables accurate adaptation to environmental changes. Incoherent FFLs that simply include protein regulators are common,10 whereas mixed FFLs are rarely known until now. Besides PrrA/PcrZ, the RpoE/RybB and PhoP/AmgR systems of E. coli and Salmonella enterica, respectively, exhibit features of incoherent FFLs. During envelope stress in E. coli RpoE is released from the membrane and induces the expression of the sRNA RybB and of about 100 other genes mainly involved in outer membrane modification and repair.11 Induction of three RpoE-dependent genes is counteracted by RybB, closing a potential incoherent FFL (Fig. 2B). In S. enterica, low magnesium concentrations lead to phosphorylation of the transcriptional regulator PhoP, which, in turn, activates the expression of mgtC and its cis-encoded sRNA AmgR simultaneously.12 AmgR counteracts mgtC expression resulting in reduced MgtC amounts (Fig. 2B).13 In all three cases (PrrA/PcrZ, RpoE/RybB and PhoP/AmgR), beneficial fine-tuning of gene expression is achieved. Another FFL is the coherent form, where the direct regulation path (X to Z) has the same outcome as the overall regulation (X over Y to Z). The four different types of coherent FFLs are illustrated in Figure 2C. Coherent FFLs can cause a sign-sensitive delay by using either AND- or OR-gates to regulate the transcription of target genes.9 In the case of an AND-gate, X and Y are required for entire Z transcription. If an OR-gate is present, X or Y is sufficient for Z transcription. Examples for mixed coherent FFLs are described in E. coli and Staphylococcus aureus. In E. coli, the sensor kinase EnvZ monitors changes in osmolarity and modulates the activity of the transcriptional regulator OmpR.14 Phosphorylated OmpR (OmpR-P) modulates the expression of its target genes ompC and ompF, encoding outer membrane proteins in a concentration-dependent manner.15,16 At high OmpR-P levels, ompC expression is activated, whereas ompF is repressed. Additionally, OmpR-P inhibits MicC and induces MicF expression, leading to an enhanced activation of ompC and an increased inhibition of ompF, respectively (Fig. 2D).16,17 The multifunctional RNAIII from S. aureus acts as both activator and repressor of mRNA translation. In stationary growth phase, the ArgA-ArgC two-component system activates transcription of RNAIII.18,19 On one hand, binding of the RNAIII 5′-end to a secondary structure, which blocks the ribosome-binding side (RBS) of hla (hemolysin α) mRNA, results in translation initiation.20 On the other hand RNAIII also binds to rot (repressor of toxins) mRNA and initiates RNase III cleavage of the sRNA/mRNA duplex.21 Since Rot represses hla, the inactivation of Rot by RNAIII further enhances transcription of hla (Fig. 2D).


A mixed incoherent feed-forward loop contributes to the regulation of bacterial photosynthesis genes.

Mank NN, Berghoff BA, Klug G - RNA Biol (2013)

Figure 2. (A and C) Structure and regulatory output of incoherent and coherent FFL motifs. Four different types (I1-I4 and C1-C4) are depicted, where X and Y refer to transcription factors (black boxes) and small RNAs (gray boxes), respectively. Z reflects target genes of X and Y, modified from Mangan and Alon.9 In the case of the RNAIII FFL, Rot stands on one hand for the rot mRNA, repressed by RNAIII, on the other hand for the Rot protein, repressing hla. (B) Schematic picture of the PrrA/PcrZ, RpoE/RybB and PhoP/AmgR mixed incoherent FFLs in R. sphaeroides, E. coli and S. enterica, respectively. (D) Schematic picture of mixed coherent FFLs. The OmpR-based and RNAIII-based FFLs from E. coli and S. aureus, respectively, are depicted.
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Related In: Results  -  Collection

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Figure 2: Figure 2. (A and C) Structure and regulatory output of incoherent and coherent FFL motifs. Four different types (I1-I4 and C1-C4) are depicted, where X and Y refer to transcription factors (black boxes) and small RNAs (gray boxes), respectively. Z reflects target genes of X and Y, modified from Mangan and Alon.9 In the case of the RNAIII FFL, Rot stands on one hand for the rot mRNA, repressed by RNAIII, on the other hand for the Rot protein, repressing hla. (B) Schematic picture of the PrrA/PcrZ, RpoE/RybB and PhoP/AmgR mixed incoherent FFLs in R. sphaeroides, E. coli and S. enterica, respectively. (D) Schematic picture of mixed coherent FFLs. The OmpR-based and RNAIII-based FFLs from E. coli and S. aureus, respectively, are depicted.
Mentions: Regulatory networks control accurate gene expression and are therefore essential to fully adapt to various stimuli like stresses or nutrient changes. One of these networks is the so-called FFL, which consists of a transcription factor X regulating a second transcription factor Y. Both protein factors jointly regulate the transcription rate of a target gene Z (Fig. 2). Whenever one of the protein factors (X or Y) is replaced by an sRNA, a post-transcriptional regulation level is inserted into the FFL. In this case it is called a mixed FFL.9 In Escherichia coli and Saccharomyces cerevisiae, one of the most common network motifs is the incoherent FFL. There are four described types of this network motif, which have in common that direct (X to Z) and indirect (X over Y to Z) regulation paths are opposite (Fig. 2A). This type of gene regulation allows for speeding up inhibition of target gene activation, which is called pulse expression.9,10 This enables accurate adaptation to environmental changes. Incoherent FFLs that simply include protein regulators are common,10 whereas mixed FFLs are rarely known until now. Besides PrrA/PcrZ, the RpoE/RybB and PhoP/AmgR systems of E. coli and Salmonella enterica, respectively, exhibit features of incoherent FFLs. During envelope stress in E. coli RpoE is released from the membrane and induces the expression of the sRNA RybB and of about 100 other genes mainly involved in outer membrane modification and repair.11 Induction of three RpoE-dependent genes is counteracted by RybB, closing a potential incoherent FFL (Fig. 2B). In S. enterica, low magnesium concentrations lead to phosphorylation of the transcriptional regulator PhoP, which, in turn, activates the expression of mgtC and its cis-encoded sRNA AmgR simultaneously.12 AmgR counteracts mgtC expression resulting in reduced MgtC amounts (Fig. 2B).13 In all three cases (PrrA/PcrZ, RpoE/RybB and PhoP/AmgR), beneficial fine-tuning of gene expression is achieved. Another FFL is the coherent form, where the direct regulation path (X to Z) has the same outcome as the overall regulation (X over Y to Z). The four different types of coherent FFLs are illustrated in Figure 2C. Coherent FFLs can cause a sign-sensitive delay by using either AND- or OR-gates to regulate the transcription of target genes.9 In the case of an AND-gate, X and Y are required for entire Z transcription. If an OR-gate is present, X or Y is sufficient for Z transcription. Examples for mixed coherent FFLs are described in E. coli and Staphylococcus aureus. In E. coli, the sensor kinase EnvZ monitors changes in osmolarity and modulates the activity of the transcriptional regulator OmpR.14 Phosphorylated OmpR (OmpR-P) modulates the expression of its target genes ompC and ompF, encoding outer membrane proteins in a concentration-dependent manner.15,16 At high OmpR-P levels, ompC expression is activated, whereas ompF is repressed. Additionally, OmpR-P inhibits MicC and induces MicF expression, leading to an enhanced activation of ompC and an increased inhibition of ompF, respectively (Fig. 2D).16,17 The multifunctional RNAIII from S. aureus acts as both activator and repressor of mRNA translation. In stationary growth phase, the ArgA-ArgC two-component system activates transcription of RNAIII.18,19 On one hand, binding of the RNAIII 5′-end to a secondary structure, which blocks the ribosome-binding side (RBS) of hla (hemolysin α) mRNA, results in translation initiation.20 On the other hand RNAIII also binds to rot (repressor of toxins) mRNA and initiates RNase III cleavage of the sRNA/mRNA duplex.21 Since Rot represses hla, the inactivation of Rot by RNAIII further enhances transcription of hla (Fig. 2D).

Bottom Line: Living cells use a variety of regulatory network motifs for accurate gene expression in response to changes in their environment or during differentiation processes.In Rhodobacter sphaeroides, a complex regulatory network controls expression of photosynthesis genes to guarantee optimal energy supply on one hand and to avoid photooxidative stress on the other hand.This point-of-view provides a comparison to other described feed-forward loops and discusses the physiological relevance of PcrZ in more detail.

View Article: PubMed Central - PubMed

Affiliation: Institut für Mikrobiologie und Molekularbiologie; Universität Giessen; Giessen, Germany.

ABSTRACT
Living cells use a variety of regulatory network motifs for accurate gene expression in response to changes in their environment or during differentiation processes. In Rhodobacter sphaeroides, a complex regulatory network controls expression of photosynthesis genes to guarantee optimal energy supply on one hand and to avoid photooxidative stress on the other hand. Recently, we identified a mixed incoherent feed-forward loop comprising the transcription factor PrrA, the sRNA PcrZ and photosynthesis target genes as part of this regulatory network. This point-of-view provides a comparison to other described feed-forward loops and discusses the physiological relevance of PcrZ in more detail.

Show MeSH