Biology:CsrA protein

From HandWiki
CsrA
CsrA dimer from Escherichia coli.[1]
Identifiers
SymbolCsrA
PfamPF02599
InterProIPR003751

Carbon storage regulator A (CsrA) is an RNA-binding protein first identified in Escherichia coli, and its homologs are found in many bacterial species and pathogens.[2] In pseudomonads, CsrA homologs are called repressor of secondary metabolites (i.e., RsmA, RsmE, and RsmF).[2][3] CsrA proteins are post-transcriptional regulators of gene expression that bind to RNA targets, impacting their transcription, translation, and/or RNA stability.[4] In the most commonly studied mechanism of regulation, CsrA binds to the Shine–Dalgarno sequence of a messenger RNA and inhibits translation initiation and facilitates mRNA decay.[5]

Across different species, CsrA regulates glycogen biosynthesis and catabolism,[6] glycolysis,[5] biofilm formation,[7] bacterial motility,[8] quorum sensing,[9] andvirulence.[2]

RNA Interactions

A consensus secondary structure and primary sequence for the targets of the CsrA RNA binding protein.

Using SELEX, the high-affinity CsrA binding motif was identified as a "GGA" sequence located in the single-stranded region of a stem-loop.[10] This binding motif was confirmed in E. coli and Salmonella using CLIP-seq.[11][12] These studies identified hundreds of target RNAs, including mRNAs, sRNAs, and tRNAs.[11][12]

CsrA activity is controlled by the expression of sRNAs such as CsrB, CsrC, RsmZ, RsmY, and RsmX that contain many copies of the CsrA binding motif.[2] These RNAs sequester CsrA, which allows the translation (or other activity) of the previously inhibited bound mRNAs.[2][4]

References

  1. Gutiérrez, P; Li, Y; Osborne, MJ; Pomerantseva, E; Liu, Q; Gehring, K (May 2005). "Solution structure of the carbon storage regulator protein CsrA from Escherichia coli.". Journal of Bacteriology 187 (10): 3496–501. doi:10.1128/JB.187.10.3496-3501.2005. PMID 15866937. 
  2. 2.0 2.1 2.2 2.3 2.4 Vakulskas, Christopher; Potts, Anastasia; Babitzke, Paul; Ahmer, Brian; Romeo, Tony (2015). "Regulation of Bacterial Virulence by Csr (Rsm) Systems". Microbiology and Molecular Biology Reviews 79 (2): 193–224. doi:10.1128/mmbr.00052-14. PMID 25833324. https://doi.org/10.1128/mmbr.00052-14. 
  3. Timmermans, J; Van Melderen, L (Sep 2010). "Post-transcriptional global regulation by CsrA in bacteria.". Cellular and Molecular Life Sciences 67 (17): 2897–908. doi:10.1007/s00018-010-0381-z. PMID 20446015. 
  4. 4.0 4.1 Pourciau, Christine; Lai, Ying-Jung; Gorelik, Mark; Babitzke, Paul; Romeo, Tony (2020-10-27). "Diverse Mechanisms and Circuitry for Global Regulation by the RNA-Binding Protein CsrA". Frontiers in Microbiology 11. doi:10.3389/fmicb.2020.601352. ISSN 1664-302X. PMID 33193284. 
  5. 5.0 5.1 Liu, MY; Gui, G; Wei, B; Preston JF, 3rd; Oakford, L; Yüksel, U; Giedroc, DP; Romeo, T (Jul 11, 1997). "The RNA molecule CsrB binds to the global regulatory protein CsrA and antagonizes its activity in Escherichia coli.". The Journal of Biological Chemistry 272 (28): 17502–10. doi:10.1074/jbc.272.28.17502. PMID 9211896. 
  6. Baker, Carol S.; Morozov, Igor; Suzuki, Kazushi; Romeo, Tony; Babitzke, Paul (2002). "CsrA regulates glycogen biosynthesis by preventing translation of glgC in Escherichia coli" (in en). Molecular Microbiology 44 (6): 1599–1610. doi:10.1046/j.1365-2958.2002.02982.x. ISSN 0950-382X. PMID 12067347. https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2958.2002.02982.x. 
  7. Jackson, DW; Suzuki, K; Oakford, L; Simecka, JW; Hart, ME; Romeo, T (Jan 2002). "Biofilm formation and dispersal under the influence of the global regulator CsrA of Escherichia coli.". Journal of Bacteriology 184 (1): 290–301. doi:10.1128/jb.184.1.290-301.2002. PMID 11741870. 
  8. Wei, Bangdong L.; Brun-Zinkernagel, Anne-Marie; Simecka, Jerry W.; Prüß, Birgit M.; Babitzke, Paul; Romeo, Tony (2001). "Positive regulation of motility and flhDC expression by the RNA-binding protein CsrA of Escherichia coli" (in en). Molecular Microbiology 40 (1): 245–256. doi:10.1046/j.1365-2958.2001.02380.x. ISSN 0950-382X. PMID 11298291. https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2958.2001.02380.x. 
  9. Sonnleitner, E; Romeo, A; Bläsi, U (Apr 2012). "Small regulatory RNAs in Pseudomonas aeruginosa.". RNA Biology 9 (4): 364–71. doi:10.4161/rna.19231. PMID 22336763. 
  10. Liu, Mu Ya; Gui, Gaojun; Wei, Bangdong; Preston, James F.; Oakford, Lawrence; Yüksel, Ümit; Giedroc, David P.; Romeo, Tony (1997). "The RNA Molecule CsrB Binds to the Global Regulatory Protein CsrA and Antagonizes Its Activity in Escherichia coli" (in en). Journal of Biological Chemistry 272 (28): 17502–17510. doi:10.1074/jbc.272.28.17502. PMID 9211896. 
  11. 11.0 11.1 Potts, Anastasia H.; Vakulskas, Christopher A.; Pannuri, Archana; Yakhnin, Helen; Babitzke, Paul; Romeo, Tony (2017-11-17). "Global role of the bacterial post-transcriptional regulator CsrA revealed by integrated transcriptomics". Nature Communications 8 (1): 1596. doi:10.1038/s41467-017-01613-1. ISSN 2041-1723. PMID 29150605. Bibcode2017NatCo...8.1596P. 
  12. 12.0 12.1 "Global RNA recognition patterns of post-transcriptional regulators Hfq and CsrA revealed by UV crosslinking in vivo.". EMBO J 35 (9): 991–1011. 2016. doi:10.15252/embj.201593360. PMID 27044921.