Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The question remains: Is the spliceosome a ribozyme?

Abstract

The two phosphoryl transfer steps of pre-mRNA splicing are catalyzed within the large ribonuclear protein machine called the spliceosome. The highly dynamic nature of the spliceosome has presented many challenges to a structural and mechanistic understanding of its catalytic core. While much evidence supports the popular hypothesis that the catalytic steps of pre-mRNA splicing are mediated by spliceosomal RNA, a role for protein in catalysis cannot yet be ruled out. A highly conserved protein, Prp8, is a component of the catalytic core. We review data consistent with the hypothesis that Prp8 functions as a cofactor to an RNA enzyme.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Spliceosome reaction and assembly.
Figure 2: Working model of RNA and Prp8 interactions in the catalytic core, and mutually exclusive interactions of U6 and U2 snRNAs in pre-assembled snRNPs.
Figure 3: A model of Prp8 binding to a tertiary RNA structure in the catalytic core.

Similar content being viewed by others

References

  1. Burge, C.B., Tuschl, T.H. & Sharp, P.A. In RNA world II (eds, Gesteland, R.F., Cech, T.R. & Atkins, J.F.) 525–560 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York; 1998).

    Google Scholar 

  2. Nilsen, T.W. Cell 78, 1–4 (1994).

    Article  CAS  Google Scholar 

  3. Nilsen, T.W. In RNA structure and function (eds, Simons, R. & Grunberg-Manago, M.) 279–307 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York; 1998).

    Google Scholar 

  4. Madhani, H.D. & Guthrie, C. Annu. Rev. Genet. 28, 1–26 (1994).

    Article  CAS  Google Scholar 

  5. Yu, Y.-T., Scharl, E.C., Smith, C.M. & Steitz, J.A. In RNA world II (eds, Gesteland, R.F., Cech, T.R. & Atkins, J.F.) 487–524 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York; 1998).

    Google Scholar 

  6. Newman, A.J. EMBO J. 16, 5797–5800 (1997).

    Article  CAS  Google Scholar 

  7. Staley, J.P. & Guthrie, C. Cell 92, 315–326 (1998).

    Article  CAS  Google Scholar 

  8. Chua, K. & Reed, R. Genes Dev. 13, 841–850 (1999).

    Article  CAS  Google Scholar 

  9. Umen, J.G. & Guthrie, C. RNA 1, 869–885 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Sontheimer, E.J. & Steitz, J.A. Science 262, 1989–1996 (1993).

    Article  CAS  Google Scholar 

  11. Parker, R. & Siliciano, P.G. Nature 361, 660–662 (1993).

    Article  CAS  Google Scholar 

  12. Madhani, H.D. & Guthrie, C. Genes Dev. 8, 1071–1086 (1994).

    Article  CAS  Google Scholar 

  13. Yarus, M. FASEB J. 7, 31–39 (1993).

    Article  CAS  Google Scholar 

  14. Narlikar, G.J. & Herschlag, D. Annu. Rev. Biochem. 66, 19–59 (1997).

    Article  CAS  Google Scholar 

  15. Pan, T., Long, D.M. & Uhlenbeck, O.C. In The RNA world (eds, Gesteland, R.F. & Atkins, J.F.) 271–301 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York; 1993).

    Google Scholar 

  16. Gordon, P.M., Sontheimer, E.J. & Piccirilli, J.A. RNA 6, 199–205 (2000).

    Article  CAS  Google Scholar 

  17. Sontheimer, E.J., Sun, S. & Piccirilli, J.A. Nature 388, 801–805 (1997).

    Article  CAS  Google Scholar 

  18. Fabrizio, P. & Abelson, J. Nucleic Acids Res. 20, 3659–3664 (1992).

    Article  CAS  Google Scholar 

  19. Yu, Y.T., Maroney, P.A., Darzynkiwicz, E. & Nilsen, T.W. RNA 1, 46–54 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Moore, M.J. & Sharp, P.A. Nature 365, 364–368 (1993).

    Article  CAS  Google Scholar 

  21. Padgett, R.A., Podar, M., Boulanger, S.C. & Perlman, P.S. Science 266, 1685–1688 (1994).

    Article  CAS  Google Scholar 

  22. Michel, F. & Ferat, J.L. Annu. Rev. Biochem. 64, 435–461 (1995).

    Article  CAS  Google Scholar 

  23. Weiner, A.M. Cell 72, 161–164 (1993).

    Article  CAS  Google Scholar 

  24. Pyle, A.M. In Catalytic RNA (eds, Eckstein, F. & Lilley, D.M.J.) 75–107 (Springer, Berlin, New York; 1996).

    Book  Google Scholar 

  25. Boudvillain, M., de Lencastre, A. & Pyle, A.M. Nature 406, 315–318 (2000).

    Article  CAS  Google Scholar 

  26. Chiara, M.D., et al. Mol. Cell. Biol. 16, 3317–3326 (1996).

    Article  CAS  Google Scholar 

  27. Dix, I., Russell, C.S., O'Keefe, R.T., Newman, A.J. & Beggs, J.D. RNA 4, 1239–1250 (1998).

    Article  CAS  Google Scholar 

  28. Vidal, V.P., Verdone, L., Mayes, A.E. & Beggs, J.D. RNA 5, 1470–1481 (1999).

    Article  CAS  Google Scholar 

  29. Reyes, J.L., Kois, P., Konforti, B.B. & Konarska, M.M. RNA 2, 213–225 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Reyes, J.L., Gustafson, H.E., Luo, H.R., Moore, M.J. & Konarska, M.M. RNA 5, 167–179 (1999).

    Article  CAS  Google Scholar 

  31. Siatecka, M., Reyes, J.L. & Konarska, M.M. Genes Dev. 13, 1983–1993 (1999).

    Article  CAS  Google Scholar 

  32. Collins, C.A. & Guthrie, C. Genes Dev. 13, 1970–1982 (1999).

    Article  CAS  Google Scholar 

  33. Umen, J.G. & Guthrie, C. Genetics 143, 723–739 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Kim, C.H. & Abelson, J. RNA 2, 995–1010 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Bone, R., Silen, J.L. & Agard, D.A. Nature 339, 191–195 (1989).

    Article  CAS  Google Scholar 

  36. Morton, A. & Matthews, B.W. Biochemistry 34, 8576–8588 (1995).

    Article  CAS  Google Scholar 

  37. Newman, A.J. EMBO J. 16, 5797–5800 (1997).

    Article  CAS  Google Scholar 

  38. Beggs, J.D., Teigelkamp, S. & Newman, A.J. J. Cell Sci. Suppl. 19, 101–105 (1995).

    Article  CAS  Google Scholar 

  39. Achsel, T., Ahrens, K., Brahms, H., Teigelkamp, S. & Luhrmann, R. Mol. Cell. Biol. 18, 6756–6766 (1998).

    Article  CAS  Google Scholar 

  40. Raghunathan, P.L. & Guthrie, C. Curr. Biol. 8, 847–855 (1998).

    Article  CAS  Google Scholar 

  41. Fabrizio, P., Laggerbauer, B., Lauber, J., Lane, W.S. & Lührmann, R. EMBO J. 16, 4092–4106 (1997).

    Article  CAS  Google Scholar 

  42. Kuhn, A.N. & Brow, D.A. Genetics 155, 1667–1682 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Kuhn, A.N., Li, Z. & Brow, D.A. Mol. Cell 3, 65–75 (1999).

    Article  CAS  Google Scholar 

  44. Staley, J.P. & Guthrie, C. Mol. Cell 3, 55–64 (1999).

    Article  CAS  Google Scholar 

  45. Strauss, E.J. & Guthrie, C. Genes Dev. 5, 629–641 (1991).

    Article  CAS  Google Scholar 

  46. Weeks, K.M. & Cech, T.R. Cell 82, 221–230 (1995).

    Article  CAS  Google Scholar 

  47. Weeks, K.M. Curr. Opin. Struct. Biol. 7, 336–342 (1997).

    Article  CAS  Google Scholar 

  48. Frankel, A.D. & Smith, C.A. Cell 92, 149–151 (1998).

    Article  CAS  Google Scholar 

  49. Williamson, J.R. Nature Struct. Biol. 7, 834–837 (2000).

    Article  CAS  Google Scholar 

  50. Bernstein, H.D. Nature Struct. Biol. 7, 179–181 (2000).

    Article  CAS  Google Scholar 

  51. Conn, G.L., Draper, D.E., Lattman, E.E. & Gittis, A.G. Science 284, 1171–1174 (1999).

    Article  CAS  Google Scholar 

  52. Valadkhan, S. & Manley, J.L. RNA 6, 206–219 (2000).

    Article  CAS  Google Scholar 

  53. Nissen, P., Hansen, J., Ban, N., Moore, P.B. & Steitz, T.A. Science 289, 920–930 (2000).

    Article  CAS  Google Scholar 

  54. Ban, N., Nissen, P., Hansen, J., Moore, P.B. & Steitz, T.A. Science 289, 905–920 (2000).

    Article  CAS  Google Scholar 

  55. Puglisi, J.D., Blanchard, S. & Green, R. Nature Struct. Biol. 7, 855–861 (2000).

    Article  CAS  Google Scholar 

  56. Sharp, P.A. & Burge, C.B. Cell 91, 875–879 (1997).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank J. Abelson, A. Kistler, M. Inada, J. Staley, S. Rader, T. Villa and R. Wagner for helpful comments and discussions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christine Guthrie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Collins, C., Guthrie, C. The question remains: Is the spliceosome a ribozyme?. Nat Struct Mol Biol 7, 850–854 (2000). https://doi.org/10.1038/79598

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/79598

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing