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Systems Biology of Bacterial Immune Systems: Regulation of Restriction-Modification and CRISPR-Cas Systems

  • Andjela Rodic
  • Bojana Blagojevic
  • Marko Djordjevic
Chapter
Part of the RNA Technologies book series (RNATECHN)

Abstract

Restriction-modification (R-M) and CRISPR-Cas are bacterial immune systems which defend their prokaryotic hosts from invasive DNA. Understanding how these systems are regulated is necessary for both biotechnology applications, and for understanding how they modulate horizontal gene transfer (including acquisition of virulence factors). We here review results on modeling these systems which point to common general principles underlying their architecture and dynamical response, with particular emphasis on modeling methods. We show that the modeling predictions are in a good agreement with both in vitro measurements of promoter transcription activity and the first in vivo measurements of gene expression dynamics in R-M systems. Modeling induction of CRISPR-Cas systems is challenging, as signaling which leads to their activation is currently unknown. However, based on similarities between transcription regulation in CRISPR-Cas and some R-M systems, we argue that transcription regulation of much simpler (and better studied) R-M systems can be used as a proxy for CRISPR-Cas transcription regulation, allowing to in silico assess CRISPR-Cas dynamical properties. Based on the obtained results, we propose that mechanistically otherwise different bacterial immune systems, presumably due to a common function, share the same unifying principles governing their expression dynamics.

Keywords

Thermodynamic modeling Restriction-modification systems CRISPR-Cas Gene expression regulation Regulatory dynamics  

References

  1. Bogdanova E, Djordjevic M, Papapanagiotou I et al (2008) Transcription regulation of the type II restriction-modification system AhdI. Nucleic Acids Res 36:1429–1442CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bogdanova E, Zakharova M, Streeter S et al (2009) Transcription regulation of restriction-modification system Esp1396I. Nucleic Acids Res 37:3354–3366CrossRefPubMedPubMedCentralGoogle Scholar
  3. Chen C-C, Fang M, Majumder A et al (2001) A 72-base pair AT-rich DNA sequence element functions as a bacterial gene silencer. J Biol Chem 276:9478–9485CrossRefPubMedGoogle Scholar
  4. Djordjevic M, Djordjevic M, Severinov K (2012) CRISPR transcript processing: a mechanism for generating a large number of small interfering RNAs. Biol Direct 7:24–34CrossRefPubMedPubMedCentralGoogle Scholar
  5. Dresch JM, Richards M, Ay A (2013) A primer on thermodynamic-based models for deciphering transcriptional regulatory logic. BBA-Gene Regul Mech 1829:946–953Google Scholar
  6. Ershova A, Rusinov I, Spirin S et al (2015) Role of restriction-modification systems in prokaryotic evolution and ecology. Biochemistry-Moscow 80:1373–1386CrossRefPubMedGoogle Scholar
  7. Goldberg GW, Marraffini LA (2015) Resistance and tolerance to foreign elements by prokaryotic immune systems – curating the genome. Nat Rev Immunol 15:717–724CrossRefPubMedPubMedCentralGoogle Scholar
  8. Hille F, Charpentier E (2016) CRISPR-Cas: biology, mechanisms and relevance. Philos T Roy Soc B 371:20150496CrossRefGoogle Scholar
  9. Künne T, Kieper SN, Bannenberg JW et al (2016) Cas3-derived target DNA degradation fragments fuel primed CRISPR adaptation. Mol Cell 63:852–864CrossRefPubMedGoogle Scholar
  10. Le Novère N (2015) Quantitative and logic modelling of molecular and gene networks. Nat Rev Genet 16:146–158CrossRefPubMedPubMedCentralGoogle Scholar
  11. McGeehan J, Papapanagiotou I, Streeter S et al (2006) Cooperative binding of the C.AhdI controller protein to the C/R promoter and its role in endonuclease gene expression. J Mol Biol 358:523–531CrossRefPubMedGoogle Scholar
  12. Medina-Aparicio L, Rebollar-Flores J, Gallego-Hernández A et al (2011) The CRISPR/Cas immune system is an operon regulated by LeuO, H-NS, and leucine-responsive regulatory protein in Salmonella enterica serovar Typhi. J Bacteriol 193:2396–2407CrossRefPubMedPubMedCentralGoogle Scholar
  13. Morozova N, Sabantsev A, Bogdanova E et al (2016) Temporal dynamics of methyltransferase and restriction endonuclease accumulation in individual cells after introducing a restriction-modification system. Nucleic Acids Res 44:790–800CrossRefPubMedGoogle Scholar
  14. Mruk I, Blumenthal RM (2008) Real-time kinetics of restriction–modification gene expression after entry into a new host cell. Nucleic Acids Res 36:2581–2593CrossRefPubMedPubMedCentralGoogle Scholar
  15. Musharova O, Klimuk E, Datsenko KA et al (2017) Spacer-length DNA intermediates are associated with Cas1 in cells undergoing primed CRISPR adaptation. Nucleic Acids Res 45:3297–3307CrossRefPubMedPubMedCentralGoogle Scholar
  16. Nagornykh M, Bogdanova E, Protsenko A et al (2008) Regulation of gene expression in a type II restriction-modification system. Russ J Genet 44:523–532CrossRefGoogle Scholar
  17. Phillips R, Kondev J, Theriot J et al (2012) Physical biology of the cell. Garland Science, New YorkCrossRefGoogle Scholar
  18. Pougach K, Semenova E, Bogdanova E et al (2010) Transcription, processing and function of CRISPR cassettes in Escherichia coli. Mol Microbiol 77:1367–1379CrossRefPubMedPubMedCentralGoogle Scholar
  19. Pul Ü, Wurm R, Arslan Z et al (2010) Identification and characterization of E. coli CRISPR-cas promoters and their silencing by H-NS. Mol Microbiol 75:1495–1512CrossRefPubMedGoogle Scholar
  20. Ratner HK, Sampson TR, Weiss DS (2015) I can see CRISPR now, even when phage are gone: a view on alternative CRISPR-Cas functions from the prokaryotic envelope. Curr Opin Infect Dis 28:267–274CrossRefPubMedPubMedCentralGoogle Scholar
  21. Rodic A, Blagojevic B, Djordjevic M et al (2017a) Features of CRISPR-Cas regulation key to highly efficient and temporally-specific crRNA production. Front Microbiol 8:2139CrossRefPubMedPubMedCentralGoogle Scholar
  22. Rodic A, Blagojevic B, Zdobnov E et al (2017b) Understanding key features of bacterial restriction-modification systems through quantitative modeling. BMC Syst Biol 11:377–391CrossRefPubMedGoogle Scholar
  23. Semenova E, Minakhin L, Bogdanova E et al (2005) Transcription regulation of the EcoRV restriction–modification system. Nucleic Acids Res 33:6942–6951CrossRefPubMedPubMedCentralGoogle Scholar
  24. Shea MA, Ackers GK (1985) The OR control system of bacteriophage lambda: a physical-chemical model for gene regulation. J Mol Biol 181:211–230CrossRefPubMedGoogle Scholar
  25. Sneppen K, Zocchi G (2005) Physics in molecular biology. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  26. Sternberg SH, Richter H, Charpentier E et al (2016) Adaptation in CRISPR-Cas systems. Mol Cell 61:797–808CrossRefPubMedGoogle Scholar
  27. Stowe K (2007) An introduction to thermodynamics and statistical mechanics. Cambridge University Press, New YorkCrossRefGoogle Scholar
  28. Stratmann T, Pul Ü, Wurm R et al (2012) RcsB-BglJ activates the Escherichia coli leuO gene, encoding an H-NS antagonist and pleiotropic regulator of virulence determinants. Mol Microbiol 83:1109–1123CrossRefPubMedGoogle Scholar
  29. Westra ER, Pul Ü, Heidrich N et al (2010) H-NS-mediated repression of CRISPR-based immunity in Escherichia coli K12 can be relieved by the transcription activator LeuO. Mol Microbiol 77:1380–1393CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Andjela Rodic
    • 1
    • 2
  • Bojana Blagojevic
    • 3
  • Marko Djordjevic
    • 1
  1. 1.Institute of Physiology and Biochemistry, Faculty of BiologyUniversity of BelgradeBelgradeSerbia
  2. 2.Multidisciplinary PhD program in BiophysicsUniversity of BelgradeBelgradeSerbia
  3. 3.Institute of PhysicsUniversity of BelgradeBelgradeSerbia

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