Letter | Published:

Base pairing between U2 and U6 snRNAs is necessary for splicing of a mammalian pre-mRNA

Naturevolume 352pages818821 (1991) | Download Citation

Subjects

Abstract

SPLICING of pre-messenger RNA in eukaryotic cells occurs in a multicomponent complex termed the spliceosome, which contains small nuclear ribonucleoprotein particles (snRNPs), protein fac-tors and substrate pre-mRNA1–3. Assembly of the spliceosome involves the stepwise binding of snRNPs and protein factors to the pre-mRNA through a poorly understood mechanism which probably involves specific RN–RNA, RNA–protein and protein–protein interactions. Of particular interest are the interactions between snRNPs, which are likely to be important not only for assembly of the spliceosome but also for catalysis. Ul snRNP interacts with the 5′ splice site and U2 snRNP with the branch site of the pre-mRNA; both of these interactions involve Watson–Crick base pairing4–9. But very little is known about how other factors such as the U4/U6 and U5 snRNPs reach the spliceosome and function in splicing. Here we report evidence that U6 snRNA interacts directly with U2 snRNA by a mechanism involving base-pairing, and that this interaction can be necessary for splicing of a mammalian pre-mRNA in vivo.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Padgett, R. A., Grabowski, P. J., Konarska, M. M., Seiler, S. & Sharp, P. A. A. Rev. Biochem. 55, 1119–1150 (1986).

  2. 2

    Maniatis, T. & Reed, R. Nature 325, 673–678 (1987).

  3. 3

    Steitz, J. A. et al. in Structure and Function of Major and Minor Small Nuclear Ribonucleoprotein Particles (ed. Birnstiel, M. L.), 115–154 (Springer, Berlin, 1988).

  4. 4

    Zhuang, Y. & Weiner, A. M. Cell 46, 827–835 (1986).

  5. 5

    Siliciano, P. G. & Guthrie, C. Genes Dev. 2, 1258–1267 (1988).

  6. 6

    Seraphin, B., Kretzner, L. & Rosbash, M. EMBO J. 7, 2533–2538 (1988).

  7. 7

    Wu, J. & Manley, J. L. Genes Dev. 3, 1553–1561 (1989).

  8. 8

    Zhuang, Y. & Weiner, A. M. Genes Dev. 3, 1545–1552 (1989).

  9. 9

    Parker, R., Siliciano, P. G. & Guthrie, C. Cell 49, 229–239 (1987).

  10. 10

    Noble, J. C. S., Pan, Z.-Q., Prives, C. & Manley, J. L. Cell 50, 227–236 (1987).

  11. 11

    Noble, J. C. S., Prives, C. & Manley, J. L. Genes Dev. 2, 1460–1475 (1988).

  12. 12

    Fu, X.-Y. & Manley, J. L. Molec. cell Biol. 7, 738–748 (1987).

  13. 13

    Fu, X.-Y., Colgan, J. D. & Manley, J. L. Molec. cell Biol. 8, 3582–3590 (1988).

  14. 14

    Black, D., Chabot, B. & Steitz, J. A. Cell 42, 737–750 (1985).

  15. 15

    Frendewey, D., Kramer, A. & Keller, W. Cold Spring Harb. Symp. quant. Biol. LII, 287–298 (1987).

  16. 16

    Hausner, T.-P., Giglio, L. M. & Weiner, A. M. Genes Dev. 4, 2146–2156 (1990).

  17. 17

    Kunkel, G. R. & Pederson, T. Genes Dev. 2, 196–204 (1988).

  18. 18

    Madhani, H. D., Bordonne, R. & Guthrie, C. Genes Dev. 4, 2264–2277 (1990).

  19. 19

    Fabrizio, P., McPheeters, D. S. & Abelson, J. Genes Dev. 3, 2137–2150 (1989).

  20. 20

    Liao, X., Kretzner, L., Seraphin, B. & Rosbash, M. Genes Dev. 4, 1766–1774 (1990).

  21. 21

    Black, D. & Steitz, J. A. Cell 46, 697–704 (1986).

  22. 22

    Vankan, P., McGuigan, C. & Mattaj, I. W. EMBO J. 9, 3397–3404 (1990).

  23. 23

    Lamond, A. I., Sproat, B., Ryder, U. & Hamm, J. Cell 58, 383–390 (1989).

  24. 24

    Blencowe, B., Sproat, B. S., Ryder, U., Barbino, S. & Lamond, A. I. Cell 59, 531–539 (1989).

  25. 25

    Guthrie, C. & Patterson, B. A. Rev. Genet. 22, 387–419 (1988).

  26. 26

    Shannon, K. W. & Guthrie, C. Genes Dev. 5, 773–785 (1991).

  27. 27

    Michel, F., Umesono, K. & Ozeki, H. Gene 82, 5–30 (1989).

  28. 28

    Sharp, P. A. Cell 42, 397–400 (1985).

  29. 29

    Cech, T. R. Cell 44, 207–210 (1986).

  30. 30

    Kunkel, T. A., Roberts, J. D. & Kakour, R. A. Meth. Enzym. 154, 367–382 (1987).

  31. 31

    Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5462–5467 (1977).

  32. 32

    Datta, B. & Weiner, A. M. Nature 352, 821–824 (1991).

Download references

Author information

Affiliations

  1. Department of Biological Sciences, Columbia University, New York, New York, 10027, USA

    • Jian Wu
    •  & James L. Manley

Authors

  1. Search for Jian Wu in:

  2. Search for James L. Manley in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/352818a0

Further reading

Comments

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.