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Split Genes and RNA Splicing (Nobel Lecture)†
Prof. Phillip A. Sharp,
Corresponding Author
Prof. Phillip A. Sharp
Department of Biology and the Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA) Telefax: Int. code + (617)253-3867
Department of Biology and the Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA) Telefax: Int. code + (619)253-3867Search for more papers by this authorProf. Phillip A. Sharp,
Corresponding Author
Prof. Phillip A. Sharp
Department of Biology and the Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA) Telefax: Int. code + (617)253-3867
Department of Biology and the Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA) Telefax: Int. code + (619)253-3867Search for more papers by this author†
Copyright © The Nobel Foundation 1994.—We thank the Nobel Foundation, Stockholm, for permission to print this lecture.
Graphical Abstract
The discovery in 1977 that genes of eukaryotic organisms contain nonsense segments (“introns”) earned P. A. Sharp the 1993 Nobel Prize for Medicine. The introns at the stage of RNA are displaced by spliceosomes or in a self-splicing process (outlined schematically below). A denotes an adenosine residue, P phosphate groups, the rectangles RNA sequences that are joined together, and the lines the intron that is spliced.
References
- 1 J. E. Darnell, Jr., Harvey Lectures 1975, 69, 1–47.
- 2 Y. Furuichi, M. Morgan, S. Muthukrishnan, A. J. Shatkin, Proc. Natl. Acad. Sci. USA 1975, 72, 362–366.
- 3 C. M. Wei, B. Moss, Proc. Natl. Acad. Sci. USA 1974, 71, 3014–3018.
- 4 F. Rottman, A. Shatkin, R. P. Perry, Cell 1974, 3, 197–199.
- 5 M. Edmonds, M. H. Vaughan, Jr., H. Nakazoto, Proc. Natl. Acad. Sci. USA 1971, 68, 1336–1340.
- 6 S. Y. Lee, J. Mendecki, G. Brawerman, Proc. Natl. Acad. Sci. USA 1971, 68, 1331–1335.
- 7 J. E. Darnell, Jr., R. Wall, R. J. Tushinski, Proc. Natl. Acad. Sci. USA 1971, 68, 1321–1325.
- 8 U. Pettersson, C. Mulder, H. Delius, P. A. Sharp, Proc. Natl. Acad. Sci. USA. 1973, 70, 200–204.
- 9
P. A. Sharp,
P. H. Gallimore,
S. J. Flint,
Cold Spring Harbor Symp. Quant. Biol.
1974,
34, 457–474.
10.1101/SQB.1974.039.01.058 Google Scholar
- 10 S. J. Flint, P. H. Gallimore, P. A. Sharp, J. Mol. Biol. 1975, 96, 47–68.
- 11 S. J. Flint, P. A. Sharp, J. Mol. Biol. 1976, 106, 749–771.
- 12 S. Bachenheimer, J. E. Darnell, Proc. Natl. Acad. Sci. USA 1975, 72, 4445–4449.
- 13 S. M. Berget, C. Moore, P. A. Sharp, Proc. Natl. Acad. Sci. USA 1977, 74, 3171–3175.
- 14 J. Lewis, J. F. Atkins, C. Anderson, P. R. Baum, R. F. Gesteland, Proc. Natl. Acad. Sci. USA 1975, 4445–4449.
- 15 M. Thomas, R. L. White, R. W. Davis, Proc. Natl. Acad. Sci. USA 1976, 73, 2294–2298.
- 16 J. Casey, N. Davidson, Nucleic Acid Res. 1977, 4, 1539–1552.
- 17 H. Westphal, J. Meyer, J. Maizel, Proc. Nail. Acad. Sci. USA 1976, 73, 2069–2071.
- 18 L. T. Chow, J. M. Roberts, J. B. Lewis, T. R. Broker, Cell 1977, 11, 819–836.
- 19 S. Goldberg, J. Weber, J. E. Darnell, Jr., Cell 1977, 10, 617–622.
- 20 J. Weber, W. Jelinek, J. E. Darnell, Jr., Cell 1977, 10, 611–611.
- 21 S. M. Berget, P. A. Sharp, J. Mol. Biol. 1979, 129, 547–565.
- 22 R. P. Perry, D. E. Kelley, Cell 1976, 8, 433–442.
- 23 R. E. Gelinas, R. J. Roberts, Cell 1977, 11, 533–544.
- 24 A. J. Jeffreys, R. A. Flavell, Cell 1977, 12, 1097–1108.
- 25 S. M. Tilghman, D. C. Tiermeier, J. G. Seidman, B. M. Peterlin, M. Sullivan, J. V. Maizel, P. Leder, Proc. Natl. Acad. Sci. USA 1978, 75, 725–729.
- 26 R. Breathnach, J-L. Manel, P. Chambon, Nature 1977, 270, 314–319.
- 27 S. Tonegawa, A. M. Maxam, R. Tizard, O. Bernard, W. Gilbert, Proc. Natl. Acad. Sci. USA 1978, 75, 1485–1489.
- 28 R. Breathnach, P. Chambon, Annu, Rev. Biochem. 1981, 50, 349–384.
- 29 R. A. Padgett, P. J. Grabowski, M. M. Konarska, S. Seiler, P. A. Sharp, Annu. Rev. Biochem. 1986, 55, 1119–1150.
- 30 G. R. Fink, Cell 1987, 49, 5–6.
- 31 R. Treisman, S. Orkin, T. Maniatis, Nature 1983, 591–596.
- 32 J. M. Nigro, K. R. Cho, E. R. Fearson, S. E. Kern, J. M. Ruppert, J. D. Oliver, D. W. Kinzler, B. Vogelstein, Cell 1991, 64, 607–613.
- 33 C. Cocquerelle, P. Daubersies, M.-A. Majerus, J.-P. Kerckaert, B. Bailleul, EMBO J. 1992, 11, 1095–1098.
- 34 R. Pulok, P. Anderson, Genes Dev. 1993, 7, 1885–1897.
- 35 R. S. Patel, E. Odermatt, J. E. Schwarzbauer, R. O. Hynes, EMBO J. 1986, 6, 2565–2572.
- 36 R. O. Hyens, Fibronectin, Springer, New York, 1989.
- 37 B. S. Baker, Nature 1989, 340, 521–524.
- 38 M. Tian, T. Maniatis, Science 1992, 256, 237–240.
- 39 W. Gilbert, Nature 1978, 271, 501.
- 40 J. E. Darnell, Jr., Science 1978, 202, 1257.
- 41 W. F. Doolittle, Nature 1978, 272, 581.
- 42 C. C. F. Blake, Nature, 1978, 273, 267.
- 43 Intervening Sequences in Evolution and Development (Ed.: E. M. Stone. R. J. Schwartz), Oxford University Press, New York, 1990.
- 44 N. Lonberg, W. Gilbert, Cell 1985, 40, 81–90.
- 45 N. Agabian, Cell 1990, 61, 1157–1160.
- 46 P. Borst, Ann. Rev. Biochem. 1986, 55, 701–732.
- 47 M. Krause, D. Hirsh, Cell 1987, 49, 753–761.
- 48 M. Vellard, A. Sureau, J. Soret, C. Martinerie, B. Perbal, Proc. Natl. Acad. Sci. USA 1992, 89, 2511–2515.
- 49 R. Benne, J. van den Burg, J. P. J. Branhenhoff, P. Sloof, J. H. van Boom, M. C. Tramp, Cell 1986, 46, 819–826.
- 50 R. A. Padgett, S. F. Hardy, P. A. Sharp, Proc. Natl. Acad. Sci. USA 1983, 80, 5230–5234.
- 51 M. R. Green, T. Maniatis, D. A. Melton, Cell 1983, 32, 681–694.
- 52 N. Hernandez, W. Keller, Cell 1983, 35, 89–99.
- 53 P. J. Grabowski, R. A. Padgett, P. A. Sharp, Cell 1984, 37, 415–427.
- 54 A. R. Krainer, T. Maniatis, B. Ruskin, M. R. Green, Cell 1984, 36, 993–1005.
- 55 M. M. Konarska, P. J. Grabowski, R. A. Padgett, P. A. Sharp, Nature 1985, 313, 552–557.
- 56 J. C. Wallace, M. Edmonds, Proc. Natl. Acad. Sci. USA 1983, 80, 950–954.
- 57 P. J. Grabowski, S. R. Seiler, P. A. Sharp, Cell 1985, 42, 345–353.
- 58 E. Brody, J. Abelson, Science 1985, 225, 963–967.
- 59
J. A. Steitz,
D. L. Black,
V. Gerke,
K. A. Parker,
A. Krämer,
D. Frendeway,
W. Keller, in
Structure and function of major and minor small nuclear ribonucleoprotein particles
(Ed.: M. L. Birnstiel),
pp. 115–154,
Springer, New York,
1988.
10.1007/978-3-642-73020-7_5 Google Scholar
- 60 T. R. Cech, Cell 1985, 43, 713–716.
- 61 C. L. Peebles, P. S. Perlman, K. L. Mecklenburg, M. L. Petrillo, J. H. Tabor, K. A. Jarrell, H.-L. Cheng, Cell 1986, 44, 213–223.
- 62 R. van der Veen, A. C. Arnberg, G. van der Horst, L. Bonen, H. F. Tabak, L. A. Grivell, Cell 1986, 44, 225–234.
- 63 P. A. Sharp, Science 1991, 254, 663.
- 64 G. J. Hannon, P. A. Maroney, J. A. Denker, T. W. Nilsen, Cell 1990, 61, 1247–1255.
- 65 K. R. Watkins, J. M. Dungan, N. Agabian, Cell 1993, in press.
- 66 M. R. Lerner, J. A. Boyle, S. M. Mount, S. L. Wolin, J. A. Steitz, Nature 1980, 283, 220–224.
- 67 J. Rogers, R. Wall, Proc. Natl. Acad. Sci. USA 1980, 77, 1877–1879.
- 68 R. A. Padgett, S. M. Mount, J. A. Steitz, P. A. Sharp, Cell 1983, 35, 101–107.
- 69 R. Parker, P. G. Siliciano, C. Guthrie, Cell 1987, 49, 229–239.
- 70 C. Guthrie, B. Patterson, Annu. Rev. Genet. 1988, 22, 387–419.
- 71 M. M. Konarska, P. A. Sharp, Cell 1987, 49, 763–774.
- 72 H. D. Madhani, C. Cuthrie, Cell 1992, 71, 803–817.
- 73 D. S. McPheeters, J. Abelson, Cell 1992, 71, 819–831.
- 74 H. Sawa, J. Abelson, Proc. Natl. Acad. Sci. USA 1992, 89, 11269–11273.
- 75 D. A. Wassarman, J. A. Steitz, Science 1992, 257, 1918–1925.
- 76 A. Newman, C. Norman, Cell 1992, 68, 743–754.
- 77 M. J. Moore, C. C. Query, P. A. Sharp, in The RNA World ( R. F. Gesteland, J. F. Atkins), Cold Spring Harbor Laboratory Press, 1993, p. 303–357.
- 78 B. Seraphin, M. Rosbash, EMBO J. 1991, 10, 1209–1216.
- 79 S. Michaud, R. Reed, Genes Dev. 1991, 5, 2534–2546.
- 80 S. F. Jamison, M. A. Garcia-Blanco, Proc. Natl. Acad. Sci. USA 1992, 89, 5482–5486.
- 81 B. Ruskin, P. D. Zamore, M. R. Green, Cell 1988, 52, 207–219.
- 82
S. W. Ruby,
J. Abelson,
Trends Genet.
1988,
7, 79–85.
10.1016/0168-9525(91)90276-V Google Scholar
- 83 C. Guthrie, Science 1991, 253, 157–163.
- 84 J. A. McSwiggen, T. R. Cech, Science 1989, 244, 679–683.
- 85 J. Rajagopal, J. A. Doudna, J. W. Szostak, Science, 1989, 244, 692–694.
- 86 E.-R. Suh, R. B. Waring, Nucleic Acids Res. 1992, 20, 6303–6309.
- 87 M. J. Moore, P. A. Sharp, Nature 1993, 365, 364–368.
- 88 M. J. Moore, P. A. Sharp, Science 1992, 256, 992–997.
- 89 A. L. Beyer, Y. N. Osheim, Genes Dev. 1988, 2, 754–765.
- 90 H. Mehlin, B. Daneholt, U. Skoglund, Cell 1992, 69, 605–613.
- 91 D. L. Specter, Annu. Rev. Cell. Biol. 1993, 9, 265–315.
- 92 U. Nyman, H. Hallman, G. Hadloczky, I. Pettersson, G. Sharp, N. R. Ringertz, J. Cell. Biol. 1986, 102, 137–144.
- 93 K. C. Carter, D. Bowman, W. Carrington, K. Fogarty, J. A. McNeil, F. S. Fay, J. B. Lawrence, Science 1993, 259, 1330–1334.
- 94 Y. Xing, C. V. Johnson, P. R. Dobner, J. B. Lawrence, Science 1993, 259, 1326–1330.
- 95 H. Ge, J. L. Manley, Cell 1990, 62, 25–34.
- 96 A. R. Krainer, G. C. Conway, D. Kozak, Cell 1990, 62, 35–42.
- 97 X.-D. Fu, T. Maniatis, Nature 1990, 343, 437–441.
- 98 S. Zeitlin, R. C. Wilson, A. Efstratiadis, J. Cell. Biol. 1989, 108, 765–777.
- 99 M. B. Roth, C. Murphy, J. G. Gall, J. Cell. Biol. 1990, 111, 2217–2223.
- 100 M. B. Roth, A. M. Zahler, J. A. Stolk, J. Cell. Biol. 1991, 115, 587–596.
- 101 B. J. Blencowe, J. A. Nickerson, R. Issner, S. Penman, P. A. Sharp, unpublished.
