CsrB sRNA family: Sequestration of RNA-binding regulatory proteins

Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Current Opinion in Microbiology (Impact Factor: 5.9). 05/2007; 10(2):156-63. DOI: 10.1016/j.mib.2007.03.007
Source: PubMed


Noncoding regulatory RNA molecules, also known as small RNAs, participate in several bacterial regulatory networks. The central component of the carbon storage regulator (Csr) and the homologous repressor of secondary metabolites (Rsm) systems is an RNA binding protein (CsrA or RsmA) that regulates gene expression post-transcriptionally by affecting ribosome binding and/or mRNA stability. Members of the CsrB family of noncoding regulatory RNA molecules contain multiple CsrA binding sites and function as CsrA antagonists by sequestering this protein. Depending on the particular organism, the Csr (or Rsm) system participates in global regulatory circuits that control central carbon flux, the production of extracellular products, cell motility, biofilm formation, quorum sensing and/or pathogenesis.

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    • "A common feature in this network present in numerous pathogenic and non-pathogenic bacteria is the transcription of at least one or more sRNAs named CsrBC or RsmYZ, depending on a two-component system (TCS). These sRNAs can interact with CsrA/RsmA and sequester it from its specific position on the target mRNA often in the immediate vicinity of the RBS (Babitzke and Romeo 2007). This leads to the translation of the previously blocked transcripts. "
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    ABSTRACT: Sequencing-based studies have illuminated increased transcriptional complexity within the genome structure of bacteria and have resulted in the identification of many small regulatory RNAs (sRNA) and a large amount of antisense transcription. It remains an open question whether these sRNAs all indeed play regulatory roles, but their identification led to an exponential increase in studies searching for their function. This allowed to show that sRNAs may modulate virulence gene expression, cellular differentiation, metabolic functions, adaptation to environmental conditions and pathogenesis. In this review we will provide mechanistic insights into how sRNAs bind mRNAs and/or proteins. Furthermore, the important roles of the RNA chaperone Hfq, the CsrA system and the CRISPR RNA will be discussed. We will then focus on sRNAs and 5(') untranslated region (UTR) elements of intracellular bacteria like Chlamydia, Listeria, Legionella, or Salmonella, and place emphasis on those that are expressed during replication in host cells and are implicated in virulence and metabolism. In addition, sRNAs that regulate motility, iron homeostasis, and differentiation or stress responses will be highlighted. Taken together sRNAs constitute key elements in many major regulatory networks governing the intracellular life and virulence of pathogenic bacteria. © FEMS 2015. All rights reserved. For permissions, please e-mail:
    FEMS microbiology reviews 05/2015; 39(3):331-349. DOI:10.1093/femsre/fuv022 · 13.24 Impact Factor
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    • "In Bacillus spp., RsaE (similar to CsrA) is involved in translation initiation of the gene hag coding for flagellin, while the protein FliW sequesters it by binding to CsrA, thus preventing CsrA activity (Romeo et al. 2013). Members of the CsrB family of noncoding regulatory RNA molecules contain multiple CsrA binding sites and function as CsrA antagonists by sequestering this protein (Babitzke and Romeo 2007, Romeo et al. 2013). "
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    ABSTRACT: The review recapitulate the current knowledge on the roles and importance of non-coding RNAs (ncRNAs) and small RNAs in bacteria. Many new RNAs have been described either in Gram positive and Gram negative bacteria, and in particular RNAs involved in pathogenesis and tolerance to stresses. The review recapitulate the current knowledge on the roles and importance of non-coding RNAs (ncRNAs) and small RNAs in bacteria. Several cases of regulating and signaling RNAs are presented either in Gram positive and Gram negative bacteria, with a focus on bacterial RNAs involved in pathogenesis and stress responses. Examples of small RNAs and their mechanisms of action, transcriptional and post-transcriptional regulation, induction of new genes, increased stability of their targets or their destination to the degradation pathway.
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    • "Similar to their Gram-negative counterparts, most sRNAs from Gram-positive species range from 50 to 250 nucleotides in length and, with notable exceptions (Balaban and Novick, 1995; Gimpel et al., 2010), do not encode for any proteins; rather, the RNA molecules themselves have intrinsic regulatory activity. For the most part, given the absence of the regulator-protein sequestering CsrB-like sRNAs from Gram-positive genomes (Babitzke and Romeo, 2007), sRNAs from Gram-positive organisms fulfil their regulatory activity by base-pairing to one or more target mRNAs, leading to an alteration in the stability and/or translation of the hybridized mRNAs. "
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    ABSTRACT: RNA-based mechanisms of regulation represent a ubiquitous class of regulators that are associated with diverse processes including nutrient sensing, stress response, modulation of horizontal gene transfer, and virulence factor expression. While better studied in Gram-negative bacteria, the literature is replete with examples of the importance of RNA-mediated regulatory mechanisms to the virulence and fitness of Gram-positives. Regulatory RNAs are classified as cis-acting, e.g. riboswitches, which modulate the transcription, translation, or stability of co-transcribed RNA, or trans-acting, e.g. small regulatory RNAs, which target separate mRNAs or proteins. The group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive bacterial pathogen from which several regulatory RNA mechanisms have been characterized. The study of RNA-mediated regulation in GAS has uncovered novel concepts with respect to how small regulatory RNAs may positively regulate target mRNA stability, and to how CRISPR RNAs are processed from longer precursors. This review provides an overview of RNA-mediated regulation in Gram-positive bacteria, and is highlighted with specific examples from GAS research. The key roles that these systems play in regulating bacterial virulence are discussed and future perspectives outlined.
    Molecular Microbiology 08/2014; 94(1). DOI:10.1111/mmi.12742 · 4.42 Impact Factor
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