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Prokaryotic Argonaute proteins: novel genome-editing tools?

Nature Reviews Microbiology volume 16, pages 5–11 (2018)Cite this article

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Abstract

Argonaute proteins constitute a highly diverse family of nucleic acid-guided proteins. They were first discovered in eukaryotes as key proteins in RNA interference systems, but homologous prokaryotic Argonaute proteins (pAgos) have also been found in archaea and bacteria. In this Progress article, we focus on long pAgo variants, a class of pAgos that are involved in nucleic acid-guided host defence against invading nucleic acids, and discuss the potential of pAgos in genome editing.

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Figure 1: Argonaute evolution and structure.
Figure 2: Prokaryotic Argonaute protein-mediated DNA interference.
Figure 3: Domain architectures of prokaryotic Argonaute proteins.

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References

  1. Bohmert, K. et al. AGO1 defines a novel locus of Arabidopsis controlling leaf development. EMBO J. 17, 170–180 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Ketting, R. F. The many faces of RNAi. Dev. Cell 20, 148–161 (2011).

    Article  CAS  PubMed  Google Scholar 

  3. Hammond, S. M., Bernstein, E., Beach, D. & Hannon, G. J. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404, 293–296 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Swarts, D. C. et al. The evolutionary journey of Argonaute proteins. Nat. Struct. Mol. Biol. 21, 743–753 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hutvagner, G. & Simard, M. J. Argonaute proteins: key players in RNA silencing. Nat. Rev. Mol. Cell Biol. 9, 22–32 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Hannon, G. J. RNA interference. Nature 418, 244–251 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Song, J. J., Smith, S. K., Hannon, G. J. & Joshua-Tor, L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305, 1434–1437 (2004).

    Article  CAS  PubMed  Google Scholar 

  8. Yuan, Y. R. et al. Crystal structure of A. aeolicus Argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. Mol. Cell 19, 405–419 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shabalina, S. A. & Koonin, E. V. Origins and evolution of eukaryotic RNA interference. Trends Ecol. Evol. 23, 578–587 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wang, Y. et al. Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes. Nature 461, 754–761 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Olovnikov, I., Chan, K., Sachidanandam, R., Newman, D. & Aravin, A. Bacterial Argonaute samples the transcriptome to identify foreign DNA. Mol. Cell 51, 594–605 (2013).

    Article  CAS  PubMed  Google Scholar 

  12. Swarts, D. C. et al. DNA-guided DNA interference by a prokaryotic Argonaute. Nature 507, 258–261 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Swarts, D. C. et al. Argonaute of the archaeon Pyrococcus furiosus is a DNA-guided nuclease that targets cognate DNA. Nucleic Acids Res. 43, 5120–5129 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kaya, E. et al. A bacterial Argonaute with noncanonical guide RNA specificity. Proc. Natl Acad. Sci. USA 113, 4057–4062 (2016).

    Article  CAS  PubMed  Google Scholar 

  15. Zander, A., Holzmeister, P., Klose, D., Tinnefeld, P. & Grohmann, D. Single-molecule FRET supports the two-state model of Argonaute action. RNA Biol. 11, 45–56 (2014).

    Article  CAS  PubMed  Google Scholar 

  16. Swarts, D. C., Koehorst, J. J., Westra, E. R., Schaap, P. J. & van der Oost, J. Effects of argonaute on gene expression in Thermus thermophilus. PLoS ONE 10, e0124880 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Willkomm, S. et al. Structural and mechanistic insights into the DNA-guided DNA endonuclease activity of an archaeal Argonaute. Nat. Microbiol. 2, 17035 (2017).

    Article  CAS  PubMed  Google Scholar 

  18. Zander, A. et al. Guide-independent DNA cleavage by archaeal Argonaute from Methanocaldococcus jannaschii. Nat. Microbiol. 2, 17034 (2017).

    Article  CAS  PubMed  Google Scholar 

  19. Swarts, D. C. et al. Autonomous generation and loading of DNA guides by bacterial Argonaute. Mol. Cell 65, 985–998 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Miyoshi, T., Ito, K., Murakami, R. & Uchiumi, T. Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute. Nat. Commun. 7, 11846 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang, Y. et al. Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature 456, 921–926 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang, Y., Sheng, G., Juranek, S., Tuschl, T. & Patel, D. J. Structure of the guide-strand-containing argonaute silencing complex. Nature 456, 209–213 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ma, J. B. et al. Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature 434, 356–372 (2015).

    Google Scholar 

  24. Song, J.-J. et al. The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes. Nat. Struct. Biol. 10, 1026–1032 (2003).

    CAS  PubMed  Google Scholar 

  25. Liu, J. et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305, 1437–1441 (2004).

    Article  CAS  PubMed  Google Scholar 

  26. Makarova, K. S., Wolf, Y. I., van der Oost, J. & Koonin, E. V. Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements. Biol. Direct 4, 29 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kwak, P. B. & Tomari, Y. The N domain of Argonaute drives duplex unwinding during RISC assembly. Nat. Struct. Mol. Biol. 19, 145–151 (2012).

    Article  CAS  PubMed  Google Scholar 

  28. Sheng, G. et al. Structure-based cleavage mechanism of Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage. Proc. Natl Acad. Sci. USA 111, 652–657 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Parker, J. S., Roe, S. M. & Barford, D. Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex. Nature 434, 663–666 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Burroughs, A. M., Iyer, L. M. & Aravind, L. Two novel PIWI families: roles in inter-genomic conflicts in bacteria and mediator-dependent modulation of transcription in eukaryotes. Biol. Direct 8, 13 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Enghiad, B. & Zhao, H. Programmable DNA-guided artificial restriction enzymes. ACS Synth. Biol. 6, 752–757 (2017).

    Article  CAS  PubMed  Google Scholar 

  32. Hsu, P. D. et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31, 827–832 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zetsche, B. et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR–Cas system. Cell 163, 759–771 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sander, J. D. & Joung, J. K. CRISPR–Cas systems for editing, regulating and targeting genomes. Nat. Biotechnol. 32, 347–355 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gao, F., Shen, X. Z., Jiang, F., Wu, Y. & Han, C. DNA-guided genome editing using the Natronobacterium gregoryi Argonaute. Nat. Biotechnol. 34, 768–772 (2016).

    Article  CAS  PubMed  Google Scholar 

  36. Cyranoski, D. Replications, ridicule and a recluse: the controversy over NgAgo gene-editing intensifies. Nature 536, 136–137 (2016).

    Article  CAS  PubMed  Google Scholar 

  37. Lee, S. H. et al. Failure to detect DNA-guided genome editing using Natronobacterium gregoryi Argonaute. Nat. Biotechnol. 35, 17–18 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Javidi-Parsijani, P. et al. No evidence of genome editing activity from Natronobacterium gregoryi Argonaute (NgAgo) in human cells. PLoS ONE 12, e0177444 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Qi, J. et al. NgAgo-based fabp11a gene knockdown causes eye developmental defects in zebrafish. Cell Res. 26, 1349–1352 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sunghyeok, Y. et al. DNA-dependent RNA cleavage by the Natronobacterium gregoryi Argonaute. Preprint at bioRxiv http://dx.doi.org/10.1101/101923 (2017).

  41. Qi, L. S. et al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152, 1173–1183 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Smalheiser, N. R. & Gomes, O. L. A. Mammalian Argonaute-DNA binding? Biol. Direct 10, 27 (2015).

    Article  Google Scholar 

  43. Blesa, A., César, C. E., Averhoff, B. & Berenguer, J. Noncanonical cell-to-cell DNA transfer in Thermus spp. is insensitive to argonaute-mediated interference. J. Bacteriol. 197, 138–146 (2015).

    Article  PubMed  Google Scholar 

  44. Averhoff, B. Shuffling genes around in hot environments: the unique DNA transporter of Thermus thermophilus. FEMS Microbiol. Rev. 33, 611–626 (2009).

    Article  CAS  Google Scholar 

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Acknowledgements

Work in the authors' laboratory was financially supported by a grant from the Netherlands Organization of Scientific Research (NWO-ECHO grant 711013002 and NWO-TOP grant 714015001) to J.v.d.O., and by a long-term postdoctoral fellowship from the European Molecular Biology Organization (EMBO) to D.C.S. (ALTF 179–2015).

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Author notes

  1. Jorrit W. Hegge and Daan C. Swarts: J.W.H and D.C.S contributed equally to this work.

Authors and Affiliations

  1. Department of Agrotechnology and Food Sciences, Laboratory of Microbiology, Wageningen University, Stippeneng 4, Wageningen, 6708WE, The Netherlands

    Jorrit W. Hegge & John van der Oost

  2. Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, Zurich, CH-8057, Switzerland

    Daan C. Swarts

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Correspondence to John van der Oost.

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Hegge, J., Swarts, D. & van der Oost, J. Prokaryotic Argonaute proteins: novel genome-editing tools?. Nat Rev Microbiol 16, 5–11 (2018). https://doi.org/10.1038/nrmicro.2017.73

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