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The true core of RNA silencing revealed

Nature Structural & Molecular Biology volume 19, pages 657–660 (2012)Cite this article

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RNA silencing is a sequence-specific gene regulation system conserved in eukaryotes, at the core of which lies the Argonaute protein family. Crystallographic studies of eukaryotic Argonaute proteins now reveal remarkably similar overall structures to their prokaryotic homologs while shedding new light on the fundamental relationship between their conformational dynamics and sophisticated strategies to silence specific targets.

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Figure 1: Overall structures of eukaryotic and prokaryotic Ago proteins.
Figure 2: Schematic representations of the new insights gained from the eukaryotic Ago protein structures.
Figure 3: Superimposition of the TtAgo, hAgo2 and KpAgo structures21,24,25,26 aligned by the PIWI domain (stereoview).

References

  1. Kawamata, T. & Tomari, Y. Trends Biochem. Sci. 35, 368–376 (2010).

    Article  CAS  Google Scholar 

  2. Lingel, A., Simon, B., Izaurralde, E. & Sattler, M. Nature 426, 465–469 (2003).

    Article  CAS  Google Scholar 

  3. Yan, K.S. et al. Nature 426, 468–474 (2003).

    Article  Google Scholar 

  4. Song, J.J. et al. Nat. Struct. Biol. 10, 1026–1032 (2003).

    Article  CAS  Google Scholar 

  5. Ma, J.B., Ye, K. & Patel, D.J. Nature 429, 318–322 (2004).

    Article  CAS  Google Scholar 

  6. Parker, J.S., Roe, S.M. & Barford, D. EMBO J. 23, 4727–4737 (2004).

    Article  CAS  Google Scholar 

  7. Lingel, A., Simon, B., Izaurralde, E. & Sattler, M. Nat. Struct. Mol. Biol. 11, 576–577 (2004).

    Article  CAS  Google Scholar 

  8. Parker, J.S., Roe, S.M. & Barford, D. Nature 434, 663–666 (2005).

    Article  CAS  Google Scholar 

  9. Ma, J.B. et al. Nature 434, 666–670 (2005).

    Article  CAS  Google Scholar 

  10. Parker, J.S., Parizotto, E.A., Wang, M., Roe, S.M. & Barford, D. Mol. Cell 33, 204–214 (2009).

    Article  CAS  Google Scholar 

  11. Frank, F., Sonenberg, N. & Nagar, B. Nature 465, 818–822 (2010).

    Article  CAS  Google Scholar 

  12. Boland, A., Tritschler, F., Heimstadt, S., Izaurralde, E. & Weichenrieder, O. EMBO Rep. 11, 522–527 (2010).

    Article  CAS  Google Scholar 

  13. Boland, A., Huntzinger, E., Schmidt, S., Izaurralde, E. & Weichenrieder, O. Proc. Natl. Acad. Sci. USA 108, 10466–10471 (2011).

    Article  CAS  Google Scholar 

  14. Tian, Y., Simanshu, D.K., Ma, J.B. & Patel, D.J. Proc. Natl. Acad. Sci. USA 108, 903–910 (2011).

    Article  CAS  Google Scholar 

  15. Zeng, L., Zhang, Q., Yan, K. & Zhou, M.M. Proteins 79, 2004–2009 (2011).

    Article  CAS  Google Scholar 

  16. Simon, B. et al. Structure 19, 172–180 (2011).

    Article  CAS  Google Scholar 

  17. Song, J.J., Smith, S.K., Hannon, G.J. & Joshua-Tor, L. Science 305, 1434–1437 (2004).

    Article  CAS  Google Scholar 

  18. Yuan, Y.R. et al. Mol. Cell 19, 405–419 (2005).

    Article  CAS  Google Scholar 

  19. Rivas, F.V. et al. Nat. Struct. Mol. Biol. 12, 340–349 (2005).

    Article  CAS  Google Scholar 

  20. Rashid, U.J. et al. J. Biol. Chem. 282, 13824–13832 (2007).

    Article  CAS  Google Scholar 

  21. Wang, Y., Sheng, G., Juranek, S., Tuschl, T. & Patel, D.J. Nature 456, 209–213 (2008).

    Article  CAS  Google Scholar 

  22. Wang, Y. et al. Nature 456, 921–926 (2008).

    Article  CAS  Google Scholar 

  23. Wang, Y. et al. Nature 461, 754–761 (2009).

    Article  CAS  Google Scholar 

  24. Schirle, N.T. & MacRae, I.J. Science 336, 1037–1040 (2012).

    Article  CAS  Google Scholar 

  25. Elkayam, E. et al. Cell (in the press).

  26. Nakanishi, K., Weinberg, D.E., Bartel, D.P. & Patel, D.J. Nature advance online publication, doi:10.1038/nature11211 (18 May 2012).

  27. Chi, S.W., Hannon, G.J. & Darnell, R.B. Nat. Struct. Mol. Biol. 19, 321–327 (2012).

    Article  CAS  Google Scholar 

  28. Nowotny, M., Gaidamakov, S.A., Crouch, R.J. & Yang, W. Cell 121, 1005–1016 (2005).

    Article  CAS  Google Scholar 

  29. Huntzinger, E. & Izaurralde, E. Nat. Rev. Genet. 12, 99–110 (2011).

    Article  CAS  Google Scholar 

  30. Eulalio, A., Helms, S., Fritzsch, C., Fauser, M. & Izaurralde, E. RNA 15, 1067–1077 (2009).

    Article  CAS  Google Scholar 

  31. Liu, J. et al. Nat. Cell Biol. 7, 1261–1266 (2005).

    Article  Google Scholar 

  32. Miyoshi, K., Okada, T.N., Siomi, H. & Siomi, M.C. RNA 15, 1282–1291 (2009).

    Article  CAS  Google Scholar 

  33. Rüdel, S. et al. Nucleic Acids Res. 39, 2330–2343 (2011).

    Article  Google Scholar 

  34. Eulalio, A., Huntzinger, E. & Izaurralde, E. Nat. Struct. Mol. Biol. 15, 346–353 (2008).

    Article  CAS  Google Scholar 

  35. Till, S. et al. Nat. Struct. Mol. Biol. 14, 897–903 (2007).

    Article  CAS  Google Scholar 

  36. Djuranovic, S. et al. Nat. Struct. Mol. Biol. 17, 144–150 (2010).

    Article  CAS  Google Scholar 

  37. Behm-Ansmant, I. et al. Genes Dev. 20, 1885–1898 (2006).

    Article  CAS  Google Scholar 

  38. Iwasaki, S. et al. Mol. Cell 39, 292–299 (2010).

    Article  CAS  Google Scholar 

  39. Iki, T. et al. Mol. Cell 39, 282–291 (2010).

    Article  CAS  Google Scholar 

  40. Kwak, P.B. & Tomari, Y. Nat. Struct. Mol. Biol. 19, 145–151 (2012).

    Article  CAS  Google Scholar 

  41. Liu, Q. et al. Science 301, 1921–1925 (2003).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank past and current members of the Tomari laboratory for helpful discussions. We are supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas ('Functional machinery for non-coding RNAs') from the Japan Ministry of Education, Culture, Sports, Science and Technology, and a Grant-in-Aid for Challenging Exploratory Research from Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Hiroshi M. Sasaki and Yukihide Tomari are at the Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.,

    Hiroshi M Sasaki & Yukihide Tomari

  2. Yukihide Tomari is also in the Department of Medical Genome Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.,

    Yukihide Tomari

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  1. Hiroshi M Sasaki
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Correspondence to Yukihide Tomari.

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Sasaki, H., Tomari, Y. The true core of RNA silencing revealed. Nat Struct Mol Biol 19, 657–660 (2012). https://doi.org/10.1038/nsmb.2302

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