Chapter 19 : Global Regulation by CsrA and Its RNA Antagonists

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The Csr (carbon storage regulator) or Rsm (repressor of stationary-phase metabolites) system is among the most extensively studied bacterial RNA-based regulatory systems. Its central component, the RNA binding protein CsrA (RsmA), was uncovered by a transposon mutagenesis screen designed to identify regulators of gene expression in the stationary phase of growth, using glycogen biosynthesis and expression as reporters ( ). Understanding of RNA binding proteins and their roles in regulation was limited at that time, but included Hfq and ribosomal proteins that mediate negative feedback by binding to their mRNAs ( ). Soon after its discovery, the regulatory role of CsrA began to emerge, which included repression of other genes similar to , which are expressed in stationary phase or under stress conditions ( ), and evidence that CsrA activates gene expression that supports robust growth ( ). Discoveries that CsrA (RsmA) regulates virulence genes of pathogens associated with plant disease ( ) and mammalian cell invasion ( ) offered early glimpses of the widespread roles played by CsrA proteins in microbe-host interactions ( ). The role of CsrA in biofilm formation ( ), quorum sensing ( ), carbon metabolism ( ), motility ( ), and stress responses ( ) is now well documented in and other species. New functions of CsrA are being uncovered at a rapid pace through the use of transcriptomics, proteomics, metabolomics, and other systems approaches ( ).

Citation: Romeo T, Babitzke P. 2019. Global Regulation by CsrA and Its RNA Antagonists, p 341-354. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0009-2017
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Image of Figure 1
Figure 1

(A) Example of a high-affinity CsrA binding site. The conserved GGA motif is in red. (B) Structure of the CsrA-RNA complex. The GGA motifs are indicated by blue boxes, and the critical L4 and R44 residues are indicated in red. Adapted from reference with permission.

Citation: Romeo T, Babitzke P. 2019. Global Regulation by CsrA and Its RNA Antagonists, p 341-354. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0009-2017
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Figure 2

Mechanisms for CsrA-mediated translational repression (A), transcription termination (B), and protection of mRNA from nuclease cleavage. Adapted from reference with permission.

Citation: Romeo T, Babitzke P. 2019. Global Regulation by CsrA and Its RNA Antagonists, p 341-354. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0009-2017
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Figure 3

Modes of CsrA antagonism. In various species, dedicated sRNAs, moonlighting sRNAs, mRNA, and/or proteins have been found to bind to CsrA and inhibit its activity.

Citation: Romeo T, Babitzke P. 2019. Global Regulation by CsrA and Its RNA Antagonists, p 341-354. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0009-2017
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Figure 4

Central regulatory circuitry of the Csr system. Dedicated components of the Csr system are highlighted in red.

Citation: Romeo T, Babitzke P. 2019. Global Regulation by CsrA and Its RNA Antagonists, p 341-354. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0009-2017
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Figure 5

Regulatory interactions of the Csr system with stringent response (A), extracytoplasmic stress (B), and carbon catabolite repression (C) global regulatory systems. Adapted from references , and with permission.

Citation: Romeo T, Babitzke P. 2019. Global Regulation by CsrA and Its RNA Antagonists, p 341-354. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0009-2017
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Table 1

CsrA and its antagonists

Citation: Romeo T, Babitzke P. 2019. Global Regulation by CsrA and Its RNA Antagonists, p 341-354. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0009-2017

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