Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1998 Apr 1;17(7):2095–2106. doi: 10.1093/emboj/17.7.2095

Human homologs of yeast prp16 and prp17 reveal conservation of the mechanism for catalytic step II of pre-mRNA splicing.

Z Zhou 1, R Reed 1
PMCID: PMC1170554  PMID: 9524131

Abstract

Pre-mRNA splicing takes place in two catalytic steps. The second step is poorly understood, especially in mammals. In yeast, the splicing factors, Prps 16, 17, 18 and Slu7 function exclusively in step II. Here we report the isolation of cDNAs encoding human Prps 16 and 17 which are 41 and 36% identical to their yeast counterparts. The Prp16 gene is essential in yeast, and we show that a chimeric yeast-human Prp16 protein rescues a yeast Prp16 knockout strain. Immunodepletion of hPrp16 from splicing extracts specifically blocks step II, and the activity can be fully restored with recombinant hPrp16. Moreover, both hPrps 16 and 17 associate with the spliceosome late in the splicing pathway. Mutations at the 3' splice site that specifically block step II do not affect the association of hPrps 16 and 17 with the spliceosome, indicating that these factors may function at a stage of step II prior to recognition of the 3' splice site. Recently, the human homologs of Prp18 and Slu7 were identified. The observation that humans contain homologs of all four known step II proteins in yeast indicates that the mechanism for catalytic step II is highly conserved.

Full Text

The Full Text of this article is available as a PDF (925.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abovich N., Liao X. C., Rosbash M. The yeast MUD2 protein: an interaction with PRP11 defines a bridge between commitment complexes and U2 snRNP addition. Genes Dev. 1994 Apr 1;8(7):843–854. doi: 10.1101/gad.8.7.843. [DOI] [PubMed] [Google Scholar]
  2. Abovich N., Rosbash M. Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell. 1997 May 2;89(3):403–412. doi: 10.1016/s0092-8674(00)80221-4. [DOI] [PubMed] [Google Scholar]
  3. Anderson K., Moore M. J. Bimolecular exon ligation by the human spliceosome. Science. 1997 Jun 13;276(5319):1712–1716. doi: 10.1126/science.276.5319.1712. [DOI] [PubMed] [Google Scholar]
  4. Ansari A., Schwer B. SLU7 and a novel activity, SSF1, act during the PRP16-dependent step of yeast pre-mRNA splicing. EMBO J. 1995 Aug 15;14(16):4001–4009. doi: 10.1002/j.1460-2075.1995.tb00071.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arenas J. E., Abelson J. N. Prp43: An RNA helicase-like factor involved in spliceosome disassembly. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):11798–11802. doi: 10.1073/pnas.94.22.11798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Arning S., Grüter P., Bilbe G., Krämer A. Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA. RNA. 1996 Aug;2(8):794–810. [PMC free article] [PubMed] [Google Scholar]
  7. Banroques J., Abelson J. N. PRP4: a protein of the yeast U4/U6 small nuclear ribonucleoprotein particle. Mol Cell Biol. 1989 Sep;9(9):3710–3719. doi: 10.1128/mcb.9.9.3710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bennett M., Michaud S., Kingston J., Reed R. Protein components specifically associated with prespliceosome and spliceosome complexes. Genes Dev. 1992 Oct;6(10):1986–2000. doi: 10.1101/gad.6.10.1986. [DOI] [PubMed] [Google Scholar]
  9. Bjørn S. P., Soltyk A., Beggs J. D., Friesen J. D. PRP4 (RNA4) from Saccharomyces cerevisiae: its gene product is associated with the U4/U6 small nuclear ribonucleoprotein particle. Mol Cell Biol. 1989 Sep;9(9):3698–3709. doi: 10.1128/mcb.9.9.3698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brown J. D., Beggs J. D. Roles of PRP8 protein in the assembly of splicing complexes. EMBO J. 1992 Oct;11(10):3721–3729. doi: 10.1002/j.1460-2075.1992.tb05457.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Burgess S., Couto J. R., Guthrie C. A putative ATP binding protein influences the fidelity of branchpoint recognition in yeast splicing. Cell. 1990 Mar 9;60(5):705–717. doi: 10.1016/0092-8674(90)90086-t. [DOI] [PubMed] [Google Scholar]
  12. Chen J. H., Lin R. J. The yeast PRP2 protein, a putative RNA-dependent ATPase, shares extensive sequence homology with two other pre-mRNA splicing factors. Nucleic Acids Res. 1990 Nov 11;18(21):6447–6447. doi: 10.1093/nar/18.21.6447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chiara M. D., Gozani O., Bennett M., Champion-Arnaud P., Palandjian L., Reed R. Identification of proteins that interact with exon sequences, splice sites, and the branchpoint sequence during each stage of spliceosome assembly. Mol Cell Biol. 1996 Jul;16(7):3317–3326. doi: 10.1128/mcb.16.7.3317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chiara M. D., Palandjian L., Feld Kramer R., Reed R. Evidence that U5 snRNP recognizes the 3' splice site for catalytic step II in mammals. EMBO J. 1997 Aug 1;16(15):4746–4759. doi: 10.1093/emboj/16.15.4746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Company M., Arenas J., Abelson J. Requirement of the RNA helicase-like protein PRP22 for release of messenger RNA from spliceosomes. Nature. 1991 Feb 7;349(6309):487–493. doi: 10.1038/349487a0. [DOI] [PubMed] [Google Scholar]
  16. Cortes J. J., Sontheimer E. J., Seiwert S. D., Steitz J. A. Mutations in the conserved loop of human U5 snRNA generate use of novel cryptic 5' splice sites in vivo. EMBO J. 1993 Dec 15;12(13):5181–5189. doi: 10.1002/j.1460-2075.1993.tb06213.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Couto J. R., Tamm J., Parker R., Guthrie C. A trans-acting suppressor restores splicing of a yeast intron with a branch point mutation. Genes Dev. 1987 Jul;1(5):445–455. doi: 10.1101/gad.1.5.445. [DOI] [PubMed] [Google Scholar]
  18. Dalrymple M. A., Petersen-Bjorn S., Friesen J. D., Beggs J. D. The product of the PRP4 gene of S. cerevisiae shows homology to beta subunits of G proteins. Cell. 1989 Sep 8;58(5):811–812. doi: 10.1016/0092-8674(89)90930-6. [DOI] [PubMed] [Google Scholar]
  19. Fabrizio P., Laggerbauer B., Lauber J., Lane W. S., Lührmann R. An evolutionarily conserved U5 snRNP-specific protein is a GTP-binding factor closely related to the ribosomal translocase EF-2. EMBO J. 1997 Jul 1;16(13):4092–4106. doi: 10.1093/emboj/16.13.4092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Frank D., Guthrie C. An essential splicing factor, SLU7, mediates 3' splice site choice in yeast. Genes Dev. 1992 Nov;6(11):2112–2124. doi: 10.1101/gad.6.11.2112. [DOI] [PubMed] [Google Scholar]
  21. Frank D., Patterson B., Guthrie C. Synthetic lethal mutations suggest interactions between U5 small nuclear RNA and four proteins required for the second step of splicing. Mol Cell Biol. 1992 Nov;12(11):5197–5205. doi: 10.1128/mcb.12.11.5197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gee S., Krauss S. W., Miller E., Aoyagi K., Arenas J., Conboy J. G. Cloning of mDEAH9, a putative RNA helicase and mammalian homologue of Saccharomyces cerevisiae splicing factor Prp43. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):11803–11807. doi: 10.1073/pnas.94.22.11803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gozani O., Patton J. G., Reed R. A novel set of spliceosome-associated proteins and the essential splicing factor PSF bind stably to pre-mRNA prior to catalytic step II of the splicing reaction. EMBO J. 1994 Jul 15;13(14):3356–3367. doi: 10.1002/j.1460-2075.1994.tb06638.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Horowitz D. S., Abelson J. A U5 small nuclear ribonucleoprotein particle protein involved only in the second step of pre-mRNA splicing in Saccharomyces cerevisiae. Mol Cell Biol. 1993 May;13(5):2959–2970. doi: 10.1128/mcb.13.5.2959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Horowitz D. S., Abelson J. Stages in the second reaction of pre-mRNA splicing: the final step is ATP independent. Genes Dev. 1993 Feb;7(2):320–329. doi: 10.1101/gad.7.2.320. [DOI] [PubMed] [Google Scholar]
  26. Horowitz D. S., Krainer A. R. A human protein required for the second step of pre-mRNA splicing is functionally related to a yeast splicing factor. Genes Dev. 1997 Jan 1;11(1):139–151. doi: 10.1101/gad.11.1.139. [DOI] [PubMed] [Google Scholar]
  27. Jones M. H., Frank D. N., Guthrie C. Characterization and functional ordering of Slu7p and Prp17p during the second step of pre-mRNA splicing in yeast. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9687–9691. doi: 10.1073/pnas.92.21.9687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kim S. H., Lin R. J. Spliceosome activation by PRP2 ATPase prior to the first transesterification reaction of pre-mRNA splicing. Mol Cell Biol. 1996 Dec;16(12):6810–6819. doi: 10.1128/mcb.16.12.6810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  30. Krämer A. The structure and function of proteins involved in mammalian pre-mRNA splicing. Annu Rev Biochem. 1996;65:367–409. doi: 10.1146/annurev.bi.65.070196.002055. [DOI] [PubMed] [Google Scholar]
  31. Lambright D. G., Sondek J., Bohm A., Skiba N. P., Hamm H. E., Sigler P. B. The 2.0 A crystal structure of a heterotrimeric G protein. Nature. 1996 Jan 25;379(6563):311–319. doi: 10.1038/379311a0. [DOI] [PubMed] [Google Scholar]
  32. Lauber J., Fabrizio P., Teigelkamp S., Lane W. S., Hartmann E., Luhrmann R. The HeLa 200 kDa U5 snRNP-specific protein and its homologue in Saccharomyces cerevisiae are members of the DEXH-box protein family of putative RNA helicases. EMBO J. 1996 Aug 1;15(15):4001–4015. [PMC free article] [PubMed] [Google Scholar]
  33. Lauber J., Plessel G., Prehn S., Will C. L., Fabrizio P., Gröning K., Lane W. S., Lührmann R. The human U4/U6 snRNP contains 60 and 90kD proteins that are structurally homologous to the yeast splicing factors Prp4p and Prp3p. RNA. 1997 Aug;3(8):926–941. [PMC free article] [PubMed] [Google Scholar]
  34. Liu Z. R., Laggerbauer B., Lührmann R., Smith C. W. Crosslinking of the U5 snRNP-specific 116-kDa protein to RNA hairpins that block step 2 of splicing. RNA. 1997 Nov;3(11):1207–1219. [PMC free article] [PubMed] [Google Scholar]
  35. Madhani H. D., Guthrie C. Dynamic RNA-RNA interactions in the spliceosome. Annu Rev Genet. 1994;28:1–26. doi: 10.1146/annurev.ge.28.120194.000245. [DOI] [PubMed] [Google Scholar]
  36. Michaud S., Reed R. A functional association between the 5' and 3' splice site is established in the earliest prespliceosome complex (E) in mammals. Genes Dev. 1993 Jun;7(6):1008–1020. doi: 10.1101/gad.7.6.1008. [DOI] [PubMed] [Google Scholar]
  37. Neer E. J., Schmidt C. J., Nambudripad R., Smith T. F. The ancient regulatory-protein family of WD-repeat proteins. Nature. 1994 Sep 22;371(6495):297–300. doi: 10.1038/371297a0. [DOI] [PubMed] [Google Scholar]
  38. Newman A. J., Norman C. U5 snRNA interacts with exon sequences at 5' and 3' splice sites. Cell. 1992 Feb 21;68(4):743–754. doi: 10.1016/0092-8674(92)90149-7. [DOI] [PubMed] [Google Scholar]
  39. Newman A. J., Teigelkamp S., Beggs J. D. snRNA interactions at 5' and 3' splice sites monitored by photoactivated crosslinking in yeast spliceosomes. RNA. 1995 Nov;1(9):968–980. [PMC free article] [PubMed] [Google Scholar]
  40. Newman A. J. The role of U5 snRNP in pre-mRNA splicing. EMBO J. 1997 Oct 1;16(19):5797–5800. doi: 10.1093/emboj/16.19.5797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Noble S. M., Guthrie C. Identification of novel genes required for yeast pre-mRNA splicing by means of cold-sensitive mutations. Genetics. 1996 May;143(1):67–80. doi: 10.1093/genetics/143.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. O'Keefe R. T., Norman C., Newman A. J. The invariant U5 snRNA loop 1 sequence is dispensable for the first catalytic step of pre-mRNA splicing in yeast. Cell. 1996 Aug 23;86(4):679–689. doi: 10.1016/s0092-8674(00)80140-3. [DOI] [PubMed] [Google Scholar]
  43. Ohno M., Shimura Y. A human RNA helicase-like protein, HRH1, facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome. Genes Dev. 1996 Apr 15;10(8):997–1007. doi: 10.1101/gad.10.8.997. [DOI] [PubMed] [Google Scholar]
  44. Ono Y., Ohno M., Shimura Y. Identification of a putative RNA helicase (HRH1), a human homolog of yeast Prp22. Mol Cell Biol. 1994 Nov;14(11):7611–7620. doi: 10.1128/mcb.14.11.7611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Patterson B., Guthrie C. A U-rich tract enhances usage of an alternative 3' splice site in yeast. Cell. 1991 Jan 11;64(1):181–187. doi: 10.1016/0092-8674(91)90219-o. [DOI] [PubMed] [Google Scholar]
  46. Patton J. G., Porro E. B., Galceran J., Tempst P., Nadal-Ginard B. Cloning and characterization of PSF, a novel pre-mRNA splicing factor. Genes Dev. 1993 Mar;7(3):393–406. doi: 10.1101/gad.7.3.393. [DOI] [PubMed] [Google Scholar]
  47. Reed R. Protein composition of mammalian spliceosomes assembled in vitro. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8031–8035. doi: 10.1073/pnas.87.20.8031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Reed R. The organization of 3' splice-site sequences in mammalian introns. Genes Dev. 1989 Dec;3(12B):2113–2123. doi: 10.1101/gad.3.12b.2113. [DOI] [PubMed] [Google Scholar]
  49. Reyes J. L., Kois P., Konforti B. B., Konarska M. M. The canonical GU dinucleotide at the 5' splice site is recognized by p220 of the U5 snRNP within the spliceosome. RNA. 1996 Mar;2(3):213–225. [PMC free article] [PubMed] [Google Scholar]
  50. Rio D. C. Accurate and efficient pre-mRNA splicing in Drosophila cell-free extracts. Proc Natl Acad Sci U S A. 1988 May;85(9):2904–2908. doi: 10.1073/pnas.85.9.2904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Schmid S. R., Linder P. D-E-A-D protein family of putative RNA helicases. Mol Microbiol. 1992 Feb;6(3):283–291. doi: 10.1111/j.1365-2958.1992.tb01470.x. [DOI] [PubMed] [Google Scholar]
  52. Schwer B., Guthrie C. A conformational rearrangement in the spliceosome is dependent on PRP16 and ATP hydrolysis. EMBO J. 1992 Dec;11(13):5033–5039. doi: 10.1002/j.1460-2075.1992.tb05610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Schwer B., Guthrie C. A dominant negative mutation in a spliceosomal ATPase affects ATP hydrolysis but not binding to the spliceosome. Mol Cell Biol. 1992 Aug;12(8):3540–3547. doi: 10.1128/mcb.12.8.3540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Schwer B., Guthrie C. PRP16 is an RNA-dependent ATPase that interacts transiently with the spliceosome. Nature. 1991 Feb 7;349(6309):494–499. doi: 10.1038/349494a0. [DOI] [PubMed] [Google Scholar]
  55. Seshadri V., Vaidya V. C., Vijayraghavan U. Genetic studies of the PRP17 gene of Saccharomyces cerevisiae: a domain essential for function maps to a nonconserved region of the protein. Genetics. 1996 May;143(1):45–55. doi: 10.1093/genetics/143.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Sikorski R. S., Boeke J. D. In vitro mutagenesis and plasmid shuffling: from cloned gene to mutant yeast. Methods Enzymol. 1991;194:302–318. doi: 10.1016/0076-6879(91)94023-6. [DOI] [PubMed] [Google Scholar]
  57. Smith C. W., Chu T. T., Nadal-Ginard B. Scanning and competition between AGs are involved in 3' splice site selection in mammalian introns. Mol Cell Biol. 1993 Aug;13(8):4939–4952. doi: 10.1128/mcb.13.8.4939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Smith C. W., Nadal-Ginard B. Mutually exclusive splicing of alpha-tropomyosin exons enforced by an unusual lariat branch point location: implications for constitutive splicing. Cell. 1989 Mar 10;56(5):749–758. doi: 10.1016/0092-8674(89)90678-8. [DOI] [PubMed] [Google Scholar]
  59. Smith C. W., Porro E. B., Patton J. G., Nadal-Ginard B. Scanning from an independently specified branch point defines the 3' splice site of mammalian introns. Nature. 1989 Nov 16;342(6247):243–247. doi: 10.1038/342243a0. [DOI] [PubMed] [Google Scholar]
  60. Sondek J., Bohm A., Lambright D. G., Hamm H. E., Sigler P. B. Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature. 1996 Jan 25;379(6563):369–374. doi: 10.1038/379369a0. [DOI] [PubMed] [Google Scholar]
  61. Sontheimer E. J., Steitz J. A. The U5 and U6 small nuclear RNAs as active site components of the spliceosome. Science. 1993 Dec 24;262(5142):1989–1996. doi: 10.1126/science.8266094. [DOI] [PubMed] [Google Scholar]
  62. Strauss E. J., Guthrie C. A cold-sensitive mRNA splicing mutant is a member of the RNA helicase gene family. Genes Dev. 1991 Apr;5(4):629–641. doi: 10.1101/gad.5.4.629. [DOI] [PubMed] [Google Scholar]
  63. Strauss E. J., Guthrie C. PRP28, a 'DEAD-box' protein, is required for the first step of mRNA splicing in vitro. Nucleic Acids Res. 1994 Aug 11;22(15):3187–3193. doi: 10.1093/nar/22.15.3187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Takagaki Y., Manley J. L. A human polyadenylation factor is a G protein beta-subunit homologue. J Biol Chem. 1992 Nov 25;267(33):23471–23474. [PubMed] [Google Scholar]
  65. Tang J., Abovich N., Fleming M. L., Seraphin B., Rosbash M. Identification and characterization of a yeast homolog of U1 snRNP-specific protein C. EMBO J. 1997 Jul 1;16(13):4082–4091. doi: 10.1093/emboj/16.13.4082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Teigelkamp S., Mundt C., Achsel T., Will C. L., Lührmann R. The human U5 snRNP-specific 100-kD protein is an RS domain-containing, putative RNA helicase with significant homology to the yeast splicing factor Prp28p. RNA. 1997 Nov;3(11):1313–1326. [PMC free article] [PubMed] [Google Scholar]
  67. Teigelkamp S., Newman A. J., Beggs J. D. Extensive interactions of PRP8 protein with the 5' and 3' splice sites during splicing suggest a role in stabilization of exon alignment by U5 snRNA. EMBO J. 1995 Jun 1;14(11):2602–2612. doi: 10.1002/j.1460-2075.1995.tb07258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Teigelkamp S., Whittaker E., Beggs J. D. Interaction of the yeast splicing factor PRP8 with substrate RNA during both steps of splicing. Nucleic Acids Res. 1995 Feb 11;23(3):320–326. doi: 10.1093/nar/23.3.320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Tronchère H., Wang J., Fu X. D. A protein related to splicing factor U2AF35 that interacts with U2AF65 and SR proteins in splicing of pre-mRNA. Nature. 1997 Jul 24;388(6640):397–400. doi: 10.1038/41137. [DOI] [PubMed] [Google Scholar]
  70. Umen J. G., Guthrie C. A novel role for a U5 snRNP protein in 3' splice site selection. Genes Dev. 1995 Apr 1;9(7):855–868. doi: 10.1101/gad.9.7.855. [DOI] [PubMed] [Google Scholar]
  71. Umen J. G., Guthrie C. Mutagenesis of the yeast gene PRP8 reveals domains governing the specificity and fidelity of 3' splice site selection. Genetics. 1996 Jun;143(2):723–739. doi: 10.1093/genetics/143.2.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Umen J. G., Guthrie C. Prp16p, Slu7p, and Prp8p interact with the 3' splice site in two distinct stages during the second catalytic step of pre-mRNA splicing. RNA. 1995 Aug;1(6):584–597. [PMC free article] [PubMed] [Google Scholar]
  73. Umen J. G., Guthrie C. The second catalytic step of pre-mRNA splicing. RNA. 1995 Nov;1(9):869–885. [PMC free article] [PubMed] [Google Scholar]
  74. Vaisman N., Tsouladze A., Robzyk K., Ben-Yehuda S., Kupiec M., Kassir Y. The role of Saccharomyces cerevisiae Cdc40p in DNA replication and mitotic spindle formation and/or maintenance. Mol Gen Genet. 1995 Apr 20;247(2):123–136. doi: 10.1007/BF00705642. [DOI] [PubMed] [Google Scholar]
  75. Vijayraghavan U., Abelson J. PRP18, a protein required for the second reaction in pre-mRNA splicing. Mol Cell Biol. 1990 Jan;10(1):324–332. doi: 10.1128/mcb.10.1.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Vijayraghavan U., Company M., Abelson J. Isolation and characterization of pre-mRNA splicing mutants of Saccharomyces cerevisiae. Genes Dev. 1989 Aug;3(8):1206–1216. doi: 10.1101/gad.3.8.1206. [DOI] [PubMed] [Google Scholar]
  77. Wall M. A., Coleman D. E., Lee E., Iñiguez-Lluhi J. A., Posner B. A., Gilman A. G., Sprang S. R. The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell. 1995 Dec 15;83(6):1047–1058. doi: 10.1016/0092-8674(95)90220-1. [DOI] [PubMed] [Google Scholar]
  78. Wassarman D. A., Steitz J. A. RNA splicing. Alive with DEAD proteins. Nature. 1991 Feb 7;349(6309):463–464. doi: 10.1038/349463a0. [DOI] [PubMed] [Google Scholar]
  79. Whittaker E., Lossky M., Beggs J. D. Affinity purification of spliceosomes reveals that the precursor RNA processing protein PRP8, a protein in the U5 small nuclear ribonucleoprotein particle, is a component of yeast spliceosomes. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2216–2219. doi: 10.1073/pnas.87.6.2216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Will C. L., Lührmann R. Protein functions in pre-mRNA splicing. Curr Opin Cell Biol. 1997 Jun;9(3):320–328. doi: 10.1016/s0955-0674(97)80003-8. [DOI] [PubMed] [Google Scholar]
  81. Wu S., Green M. R. Identification of a human protein that recognizes the 3' splice site during the second step of pre-mRNA splicing. EMBO J. 1997 Jul 16;16(14):4421–4432. doi: 10.1093/emboj/16.14.4421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Wyatt J. R., Sontheimer E. J., Steitz J. A. Site-specific cross-linking of mammalian U5 snRNP to the 5' splice site before the first step of pre-mRNA splicing. Genes Dev. 1992 Dec;6(12B):2542–2553. doi: 10.1101/gad.6.12b.2542. [DOI] [PubMed] [Google Scholar]
  83. Xu D., Nouraini S., Field D., Tang S. J., Friesen J. D. An RNA-dependent ATPase associated with U2/U6 snRNAs in pre-mRNA splicing. Nature. 1996 Jun 20;381(6584):709–713. doi: 10.1038/381709a0. [DOI] [PubMed] [Google Scholar]
  84. Zamore P. D., Patton J. G., Green M. R. Cloning and domain structure of the mammalian splicing factor U2AF. Nature. 1992 Feb 13;355(6361):609–614. doi: 10.1038/355609a0. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES