Letter | Published:

Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle

Naturevolume 409pages539542 (2001) | Download Citation



In eukaryotic cells, freshly synthesized messenger RNA (pre-mRNA) contains stretches of non-coding RNA that must be excised before the RNA can be translated into protein. Their removal is catalysed by the spliceosome, a large complex formed when a number of small nuclear ribonucleoprotein particles (snRNPs) bind sequentially to the pre-mRNA. The first snRNP to bind is called U1; other snRNPs (U2, U4/U6 and U5) follow1. Here we describe the three-dimensional structure of human U1 snRNP, determined by single-particle electron cryomicroscopy at 10 Å resolution. The reconstruction reveals a doughnut-shaped central element that accommodates the seven Sm proteins common to all snRNPs, supporting a proposed model of circular Sm protein arrangement2. By taking earlier biochemical results into account, we were able to assign the remaining density of the map to the other known components of U1 snRNP, deriving a structural model that describes the three-dimensional arrangement of proteins and RNA in U1 snRNP.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopfstrasse 2, 35037 Marburg, Germany

Max-Planck-Institut für biophysikalische Chemie, Am Fassberg 11, 37077Göttingen, Germany


  1. 1

    Moore, M. J., Query, C. C. & Sharp, P. A. in The RNA World (eds Gesteland, R. F. & Atkins, J. F.) 303–357 (Cold Spring Harbor Laboratory, Cold Spring Harbor, 1993).

  2. 2

    Kambach, C. et al. Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell 96, 375–387 (1999).

  3. 3

    Gunderson, S. I., Polycarpou-Schwarz, M. & Mattaj, I. W. U1 snRNP inhibits pre-mRNA polyadenylation through a direct interaction between U1 70K and poly(A) polymerase. Mol. Cell 1, 255–264 (1998).

  4. 4

    Casciola-Rosen, L. et al. Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death. J. Exp. Med. 183, 1957–1964 (1996).

  5. 5

    van Venrooij, W. J. & Pruijn, G. J. M. Ribonucleoprotein complexes as autoantigens. Curr. Opin. Immunol. 7, 819–824 (1995).

  6. 6

    Kastner, B., Bach, M. & Lührmann, R. Electron microscopy of small nuclear ribonucleoprotein (snRNP) particles U2 and U5: evidence for a common structure-determining principle in the major U snRNP family. Proc. Natl Acad. Sci. USA 87, 1710–1714 (1990).

  7. 7

    Raker, V. A., Hartmuth, K., Kastner, B. & Lührmann, R. Spliceosomal U snRNP core assembly: Sm proteins assemble onto an Sm site RNA nonanucleotide in a specific and thermodynamically stable manner. Mol. Cell. Biol. 19, 6554–6565 (1999).

  8. 8

    Kambach, C., Walke, S. & Nagai, K. Structure and assembly of the spliceosomal small nuclear ribonucleoprotein particles. Curr. Opin. Struct. Biol. 9, 222–230 (1999).

  9. 9

    Raker, V. A., Plessel, G. & Lührmann, R. The snRNP core assembly pathway: identification of stable core protein heteromeric complexes and an snRNP subcore particle in vitro. EMBO J. 15, 2256–2269 (1996).

  10. 10

    Will, C. L. & Lührmann, R. Protein functions in pre-mRNA splicing. Curr. Opin. Cell Biol. 9, 320–328 (1997).

  11. 11

    Nagai, K. & Mattaj, I. W. RNA-Protein Interactions in the Splicing snRNPs (eds Nagai, K. & Mattaj, I. W.) 150–177 (Oxford Univ. Press, Oxford, 1994).

  12. 12

    Oubridge, C., Ito, N., Evans, P. R., Teo, C. H. & Nagai, K. Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin. Nature 372, 432–438 (1994).

  13. 13

    Nelissen, R. L., Will, C. L., van Venrooij, W. J. & Lührmann, R. The association of the U1-specific 70K and C proteins with U1 snRNPs is mediated in part by common U snRNP proteins. EMBO J. 13, 4113–4125 (1994).

  14. 14

    Tazi, J. et al. Thiophosphorylation of U1–70K protein inhibits pre-mRNA splicing. Nature 363, 283–286 (1993).

  15. 15

    Henderson, R. The potential and limitations of neutrons, electrons and X-rays for atomic resolution microscopy of unstained biological molecules. Q. Rev. Biophys. 28, 171–193 (1995).

  16. 16

    Kastner, B., Kornstädt, U., Bach, M. & Lührmann, R. Structure of the small nuclear RNP particle U1: identification of the two structural protuberances with RNP-antigens A and 70K. J. Cell Biol. 116, 839–849 (1992).

  17. 17

    Krol, A. et al. Solution structure of human U1 snRNA. Derivation of a possible three-dimensional model. Nucleic Acids Res. 18, 3803–3811 (1990).

  18. 18

    Duckett, D. R., Murchie, A. I. & Lilley, D. M. The global folding of four-way helical junctions in RNA, including that in U1 snRNA. Cell 83, 1027–1036 (1995).

  19. 19

    Walter, F., Murchie, A. I., Duckett, D. R. & Lilley, D. M. Global structure of four-way RNA junctions studied using fluorescence resonance energy transfer. RNA 4, 719–728 (1998).

  20. 20

    Liautard, J. -P., Sri-Widada, J., Brunel, C. & Jeanteur, P. Structural organisation of ribonucleoproteins containing small nuclear RNAs from HeLa cells. J. Mol. Biol. 162, 623–643 (1982).

  21. 21

    Hartmuth, K., Raker, V. A., Huber, J., Branlant, C. & Lührmann, R. An unusual chemical reactivity of Sm site adenosines strongly correlates with proper assembly of core U snRNP particles. J. Mol. Biol. 285, 133–147 (1999).

  22. 22

    Hoet, R. M., Kastner, B., Lührmann, R. & van Venrooij, W. J. Purification and characterization of human autoantibodies directed to specific regions on U1RNA; recognition of native U1RNP complexes. Nucleic Acids Res. 21, 5130–5136 (1993).

  23. 23

    Lin, W. -L. & Pederson, T. Ribonucleoprotein organization of eukaryotic RNA. XXXI. Structure of the U1 small nuclear ribonucleoprotein. J. Mol. Biol. 180, 947–960 (1984).

  24. 24

    Urlaub, H., Raker, V., Kostka, S. & Lührmann, R. Sm protein–Sm site RNA interactions within the inner ring of the spliceosomal snRNP core structure. EMBO J. 20, 1–10 (2001).

  25. 25

    Heinrichs, V., Bach, M., Winckelmann, G. & Lührmann, R. U1-specific protein C needed for efficient complex formation of U1 snRNP with a 5′ splice site. Science 247, 69–72 (1990).

  26. 26

    Adrian, M., Dubochet, J., Lepault, J. & McDowall, A. W. Cryo-electron microscopy of viruses. Nature 308, 32–36 (1984).

  27. 27

    van Heel, M., Harauz, G. & Orlova, E. V. A new generation of the IMAGIC image processing system. J. Struct. Biol. 116, 17–24 (1996).

  28. 28

    van Heel, M. & Frank, J. Use of multivariate statistics in analysing the images of biological macromolecules. Ultramicroscopy 6, 187–194 (1981).

  29. 29

    van Heel, M. & Harauz, G. Resolution criteria for three-dimensional reconstruction. Optik 73, 119–122 (1986).

Download references


We thank F. Müller for the modelling software ERNA-3D; K. Nagai and C. Kambach for the Sm protein ring model; and M. Golas and B. Sander for assistance in electron microscopy. This work was supported by the Gottfried Wilhelm Leibniz Program and a grant from the Deutsche Forschungsgemeinschaft.


  1. Search for Holger Stark in:

  2. Search for Prakash Dube in:

  3. Search for Reinhard Lührmann in:

  4. Search for Berthold Kastner in:

About this article

Publication history



Issue Date



Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.