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. 1996 Jan;70(1):108–118. doi: 10.1128/jvi.70.1.108-118.1996

The herpes simplex virus type 1 regulatory protein ICP27 coimmunoprecipitates with anti-Sm antiserum, and the C terminus appears to be required for this interaction.

R M Sandri-Goldin 1, M K Hibbard 1
PMCID: PMC189794  PMID: 8523514

Abstract

The herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein ICP27 is required for the inhibition of host cell splicing during viral infection and for the reorganization of antigens associated with the small nuclear ribonucleoprotein particles (snRNPs). To determine what effect ICP27 had on splicing proteins that might cause their redistribution, we looked at proteins that were immunoprecipitated with anti-Sm antisera. No significant changes were seen in the migration or amounts of several snRNP common and snRNP-specific proteins from infected cells labeled with [35S]methionine, suggesting that the synthesis of these proteins was not altered by viral infection. However, when cells were labeled with 32Pi, differences were seen in the phosphorylation of at least two proteins depending on whether ICP27 was expressed. One protein, which had an apparent molecular mass of about 85 kDa, was highly phosphorylated during wild-type HSV-1 infection but much less so during infection with an ICP27 null mutant. The other protein, which migrated at the position of the U1 70-kDa protein and was precipitated with U1-specific antiserum, was also more highly phosphorylated when ICP27 was expressed during infection. Furthermore, a phosphoprotein with an apparent molecular mass of 63 kDa was found to coimmunoprecipitate with anti-Sm antisera during wild-type HSV-1 infection. ICP27 has an apparent molecular mass of 63 kDa, and immunoblot analysis confirmed that ICP27 coimmunoprecipitated with snRNPs. Analysis of mutations throughout the ICP27 protein demonstrated that the region that was required for this interaction was the C terminus of the protein, which includes a cysteine-histidine-rich region that resembles a zinc-finger-like motif. These data suggest that ICP27 interacts with snRNPs during infection and that it fosters changes in the phosphorylation state of at least two proteins that immunoprecipitate with snRNPs, although these studies do not demonstrate whether it does so directly or indirectly.

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Selected References

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  1. Amrein H., Hedley M. L., Maniatis T. The role of specific protein-RNA and protein-protein interactions in positive and negative control of pre-mRNA splicing by Transformer 2. Cell. 1994 Feb 25;76(4):735–746. doi: 10.1016/0092-8674(94)90512-6. [DOI] [PubMed] [Google Scholar]
  2. Bach M., Krol A., Lührmann R. Structure-probing of U1 snRNPs gradually depleted of the U1-specific proteins A, C and 70k. Evidence that A interacts differentially with developmentally regulated mouse U1 snRNA variants. Nucleic Acids Res. 1990 Feb 11;18(3):449–457. doi: 10.1093/nar/18.3.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Behrens S. E., Tyc K., Kastner B., Reichelt J., Lührmann R. Small nuclear ribonucleoprotein (RNP) U2 contains numerous additional proteins and has a bipartite RNP structure under splicing conditions. Mol Cell Biol. 1993 Jan;13(1):307–319. doi: 10.1128/mcb.13.1.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berget S. M. Exon recognition in vertebrate splicing. J Biol Chem. 1995 Feb 10;270(6):2411–2414. doi: 10.1074/jbc.270.6.2411. [DOI] [PubMed] [Google Scholar]
  5. Besse S., Vigneron M., Pichard E., Puvion-Dutilleul F. Synthesis and maturation of viral transcripts in herpes simplex virus type 1 infected HeLa cells: the role of interchromatin granules. Gene Expr. 1995;4(3):143–161. [PMC free article] [PubMed] [Google Scholar]
  6. Billings P. B., Hoch S. O. Characterization of U small nuclear RNA-associated proteins. J Biol Chem. 1984 Oct 25;259(20):12850–12856. [PubMed] [Google Scholar]
  7. Birney E., Kumar S., Krainer A. R. Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors. Nucleic Acids Res. 1993 Dec 25;21(25):5803–5816. doi: 10.1093/nar/21.25.5803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bridge E., Carmo-Fonseca M., Lamond A., Pettersson U. Nuclear organization of splicing small nuclear ribonucleoproteins in adenovirus-infected cells. J Virol. 1993 Oct;67(10):5792–5802. doi: 10.1128/jvi.67.10.5792-5802.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carmo-Fonseca M., Pepperkok R., Carvalho M. T., Lamond A. I. Transcription-dependent colocalization of the U1, U2, U4/U6, and U5 snRNPs in coiled bodies. J Cell Biol. 1992 Apr;117(1):1–14. doi: 10.1083/jcb.117.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cavaloc Y., Popielarz M., Fuchs J. P., Gattoni R., Stévenin J. Characterization and cloning of the human splicing factor 9G8: a novel 35 kDa factor of the serine/arginine protein family. EMBO J. 1994 Jun 1;13(11):2639–2649. doi: 10.1002/j.1460-2075.1994.tb06554.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chapman C. J., Harris J. D., Hardwicke M. A., Sandri-Goldin R. M., Collins M. K., Latchman D. S. Promoter-independent activation of heterologous virus gene expression by the herpes simplex virus immediate-early protein ICP27. Virology. 1992 Feb;186(2):573–578. doi: 10.1016/0042-6822(92)90023-i. [DOI] [PubMed] [Google Scholar]
  12. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fortes P., Lamond A. I., Ortín J. Influenza virus NS1 protein alters the subnuclear localization of cellular splicing components. J Gen Virol. 1995 Apr;76(Pt 4):1001–1007. doi: 10.1099/0022-1317-76-4-1001. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Fu X. D., Maniatis T. Factor required for mammalian spliceosome assembly is localized to discrete regions in the nucleus. Nature. 1990 Feb 1;343(6257):437–441. doi: 10.1038/343437a0. [DOI] [PubMed] [Google Scholar]
  16. Fu X. D., Maniatis T. The 35-kDa mammalian splicing factor SC35 mediates specific interactions between U1 and U2 small nuclear ribonucleoprotein particles at the 3' splice site. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1725–1729. doi: 10.1073/pnas.89.5.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fu X. D. Specific commitment of different pre-mRNAs to splicing by single SR proteins. Nature. 1993 Sep 2;365(6441):82–85. doi: 10.1038/365082a0. [DOI] [PubMed] [Google Scholar]
  18. Green M. R. Biochemical mechanisms of constitutive and regulated pre-mRNA splicing. Annu Rev Cell Biol. 1991;7:559–599. doi: 10.1146/annurev.cb.07.110191.003015. [DOI] [PubMed] [Google Scholar]
  19. Gui J. F., Lane W. S., Fu X. D. A serine kinase regulates intracellular localization of splicing factors in the cell cycle. Nature. 1994 Jun 23;369(6482):678–682. doi: 10.1038/369678a0. [DOI] [PubMed] [Google Scholar]
  20. Gui J. F., Tronchère H., Chandler S. D., Fu X. D. Purification and characterization of a kinase specific for the serine- and arginine-rich pre-mRNA splicing factors. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10824–10828. doi: 10.1073/pnas.91.23.10824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Habets W. J., Hoet M. H., De Jong B. A., Van der Kemp A., Van Venrooij W. J. Mapping of B cell epitopes on small nuclear ribonucleoproteins that react with human autoantibodies as well as with experimentally-induced mouse monoclonal antibodies. J Immunol. 1989 Oct 15;143(8):2560–2566. [PubMed] [Google Scholar]
  22. Hackl W., Fischer U., Lührmann R. A 69-kD protein that associates reversibly with the Sm core domain of several spliceosomal snRNP species. J Cell Biol. 1994 Feb;124(3):261–272. doi: 10.1083/jcb.124.3.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hardwicke M. A., Sandri-Goldin R. M. The herpes simplex virus regulatory protein ICP27 contributes to the decrease in cellular mRNA levels during infection. J Virol. 1994 Aug;68(8):4797–4810. doi: 10.1128/jvi.68.8.4797-4810.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hardwicke M. A., Vaughan P. J., Sekulovich R. E., O'Conner R., Sandri-Goldin R. M. The regions important for the activator and repressor functions of herpes simplex virus type 1 alpha protein ICP27 map to the C-terminal half of the molecule. J Virol. 1989 Nov;63(11):4590–4602. doi: 10.1128/jvi.63.11.4590-4602.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hardy W. R., Sandri-Goldin R. M. Herpes simplex virus inhibits host cell splicing, and regulatory protein ICP27 is required for this effect. J Virol. 1994 Dec;68(12):7790–7799. doi: 10.1128/jvi.68.12.7790-7799.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hermann H., Fabrizio P., Raker V. A., Foulaki K., Hornig H., Brahms H., Lührmann R. snRNP Sm proteins share two evolutionarily conserved sequence motifs which are involved in Sm protein-protein interactions. EMBO J. 1995 May 1;14(9):2076–2088. doi: 10.1002/j.1460-2075.1995.tb07199.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hibbard M. K., Sandri-Goldin R. M. Arginine-rich regions succeeding the nuclear localization region of the herpes simplex virus type 1 regulatory protein ICP27 are required for efficient nuclear localization and late gene expression. J Virol. 1995 Aug;69(8):4656–4667. doi: 10.1128/jvi.69.8.4656-4667.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Jiménez-García L. F., Spector D. L. In vivo evidence that transcription and splicing are coordinated by a recruiting mechanism. Cell. 1993 Apr 9;73(1):47–59. doi: 10.1016/0092-8674(93)90159-n. [DOI] [PubMed] [Google Scholar]
  29. Kim Y. J., Zuo P., Manley J. L., Baker B. S. The Drosophila RNA-binding protein RBP1 is localized to transcriptionally active sites of chromosomes and shows a functional similarity to human splicing factor ASF/SF2. Genes Dev. 1992 Dec;6(12B):2569–2579. doi: 10.1101/gad.6.12b.2569. [DOI] [PubMed] [Google Scholar]
  30. Kohtz J. D., Jamison S. F., Will C. L., Zuo P., Lührmann R., Garcia-Blanco M. A., Manley J. L. Protein-protein interactions and 5'-splice-site recognition in mammalian mRNA precursors. Nature. 1994 Mar 10;368(6467):119–124. doi: 10.1038/368119a0. [DOI] [PubMed] [Google Scholar]
  31. Krainer A. R., Conway G. C., Kozak D. Purification and characterization of pre-mRNA splicing factor SF2 from HeLa cells. Genes Dev. 1990 Jul;4(7):1158–1171. doi: 10.1101/gad.4.7.1158. [DOI] [PubMed] [Google Scholar]
  32. Krainer A. R., Conway G. C., Kozak D. The essential pre-mRNA splicing factor SF2 influences 5' splice site selection by activating proximal sites. Cell. 1990 Jul 13;62(1):35–42. doi: 10.1016/0092-8674(90)90237-9. [DOI] [PubMed] [Google Scholar]
  33. Lerner E. A., Lerner M. R., Janeway C. A., Jr, Steitz J. A. Monoclonal antibodies to nucleic acid-containing cellular constituents: probes for molecular biology and autoimmune disease. Proc Natl Acad Sci U S A. 1981 May;78(5):2737–2741. doi: 10.1073/pnas.78.5.2737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lerner M. R., Steitz J. A. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5495–5499. doi: 10.1073/pnas.76.11.5495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lührmann R., Kastner B., Bach M. Structure of spliceosomal snRNPs and their role in pre-mRNA splicing. Biochim Biophys Acta. 1990 Nov 30;1087(3):265–292. doi: 10.1016/0167-4781(90)90001-i. [DOI] [PubMed] [Google Scholar]
  36. Martin T. E., Barghusen S. C., Leser G. P., Spear P. G. Redistribution of nuclear ribonucleoprotein antigens during herpes simplex virus infection. J Cell Biol. 1987 Nov;105(5):2069–2082. doi: 10.1083/jcb.105.5.2069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Mayrand S. H., Dwen P., Pederson T. Serine/threonine phosphorylation regulates binding of C hnRNP proteins to pre-mRNA. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7764–7768. doi: 10.1073/pnas.90.16.7764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. McLauchlan J., Phelan A., Loney C., Sandri-Goldin R. M., Clements J. B. Herpes simplex virus IE63 acts at the posttranscriptional level to stimulate viral mRNA 3' processing. J Virol. 1992 Dec;66(12):6939–6945. doi: 10.1128/jvi.66.12.6939-6945.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Mears W. E., Lam V., Rice S. A. Identification of nuclear and nucleolar localization signals in the herpes simplex virus regulatory protein ICP27. J Virol. 1995 Feb;69(2):935–947. doi: 10.1128/jvi.69.2.935-947.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Mermoud J. E., Cohen P. T., Lamond A. I. Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism. EMBO J. 1994 Dec 1;13(23):5679–5688. doi: 10.1002/j.1460-2075.1994.tb06906.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Mermoud J. E., Cohen P., Lamond A. I. Ser/Thr-specific protein phosphatases are required for both catalytic steps of pre-mRNA splicing. Nucleic Acids Res. 1992 Oct 25;20(20):5263–5269. doi: 10.1093/nar/20.20.5263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Mosca J. D., Pitha P. M., Hayward G. S. Herpes simplex virus infection selectively stimulates accumulation of beta interferon reporter gene mRNA by a posttranscriptional mechanism. J Virol. 1992 Jun;66(6):3811–3822. doi: 10.1128/jvi.66.6.3811-3822.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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. 1994 Sep 1;13(17):4113–4125. doi: 10.1002/j.1460-2075.1994.tb06729.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. O'Keefe R. T., Mayeda A., Sadowski C. L., Krainer A. R., Spector D. L. Disruption of pre-mRNA splicing in vivo results in reorganization of splicing factors. J Cell Biol. 1994 Feb;124(3):249–260. doi: 10.1083/jcb.124.3.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Ohosone Y., Mimori T., Griffith A., Akizuki M., Homma M., Craft J., Hardin J. A. Molecular cloning of cDNA encoding Sm autoantigen: derivation of a cDNA for a B polypeptide of the U series of small nuclear ribonucleoprotein particles. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4249–4253. doi: 10.1073/pnas.86.11.4249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Pettersson I., Hinterberger M., Mimori T., Gottlieb E., Steitz J. A. The structure of mammalian small nuclear ribonucleoproteins. Identification of multiple protein components reactive with anti-(U1)ribonucleoprotein and anti-Sm autoantibodies. J Biol Chem. 1984 May 10;259(9):5907–5914. [PubMed] [Google Scholar]
  47. Phelan A., Carmo-Fonseca M., McLaughlan J., Lamond A. I., Clements J. B. A herpes simplex virus type 1 immediate-early gene product, IE63, regulates small nuclear ribonucleoprotein distribution. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9056–9060. doi: 10.1073/pnas.90.19.9056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Romac J. M., Keene J. D. Overexpression of the arginine-rich carboxy-terminal region of U1 snRNP 70K inhibits both splicing and nucleocytoplasmic transport of mRNA. Genes Dev. 1995 Jun 1;9(11):1400–1410. doi: 10.1101/gad.9.11.1400. [DOI] [PubMed] [Google Scholar]
  49. Roth M. B., Zahler A. M., Stolk J. A. A conserved family of nuclear phosphoproteins localized to sites of polymerase II transcription. J Cell Biol. 1991 Nov;115(3):587–596. doi: 10.1083/jcb.115.3.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Ruskin B., Zamore P. D., Green M. R. A factor, U2AF, is required for U2 snRNP binding and splicing complex assembly. Cell. 1988 Jan 29;52(2):207–219. doi: 10.1016/0092-8674(88)90509-0. [DOI] [PubMed] [Google Scholar]
  51. Sandri-Goldin R. M., Hibbard M. K., Hardwicke M. A. The C-terminal repressor region of herpes simplex virus type 1 ICP27 is required for the redistribution of small nuclear ribonucleoprotein particles and splicing factor SC35; however, these alterations are not sufficient to inhibit host cell splicing. J Virol. 1995 Oct;69(10):6063–6076. doi: 10.1128/jvi.69.10.6063-6076.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sandri-Goldin R. M., Mendoza G. E. A herpesvirus regulatory protein appears to act post-transcriptionally by affecting mRNA processing. Genes Dev. 1992 May;6(5):848–863. doi: 10.1101/gad.6.5.848. [DOI] [PubMed] [Google Scholar]
  53. Schröder H. C., Falke D., Weise K., Bachmann M., Carmo-Fonseca M., Zaubitzer T., Müller W. E. Change of processing and nucleocytoplasmic transport of mRNA in HSV-1-infected cells. Virus Res. 1989 May;13(1):61–78. doi: 10.1016/0168-1702(89)90087-7. [DOI] [PubMed] [Google Scholar]
  54. Shamoo Y., Abdul-Manan N., Williams K. R. Multiple RNA binding domains (RBDs) just don't add up. Nucleic Acids Res. 1995 Mar 11;23(5):725–728. doi: 10.1093/nar/23.5.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Smith I. L., Hardwicke M. A., Sandri-Goldin R. M. Evidence that the herpes simplex virus immediate early protein ICP27 acts post-transcriptionally during infection to regulate gene expression. Virology. 1992 Jan;186(1):74–86. doi: 10.1016/0042-6822(92)90062-t. [DOI] [PubMed] [Google Scholar]
  56. Smith I. L., Sandri-Goldin R. M. Evidence that transcriptional control is the major mechanism of regulation for the glycoprotein D gene in herpes simplex virus type 1-infected cells. J Virol. 1988 Apr;62(4):1474–1477. doi: 10.1128/jvi.62.4.1474-1477.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Smith I. L., Sekulovich R. E., Hardwicke M. A., Sandri-Goldin R. M. Mutations in the activation region of herpes simplex virus regulatory protein ICP27 can be trans dominant. J Virol. 1991 Jul;65(7):3656–3666. doi: 10.1128/jvi.65.7.3656-3666.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Spector D. L. Colocalization of U1 and U2 small nuclear RNPs by immunocytochemistry. Biol Cell. 1984;51(1):109–112. doi: 10.1111/j.1768-322x.1984.tb00289.x. [DOI] [PubMed] [Google Scholar]
  59. Spector D. L., Fu X. D., Maniatis T. Associations between distinct pre-mRNA splicing components and the cell nucleus. EMBO J. 1991 Nov;10(11):3467–3481. doi: 10.1002/j.1460-2075.1991.tb04911.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Spector D. L. Higher order nuclear organization: three-dimensional distribution of small nuclear ribonucleoprotein particles. Proc Natl Acad Sci U S A. 1990 Jan;87(1):147–151. doi: 10.1073/pnas.87.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Spector D. L. Macromolecular domains within the cell nucleus. Annu Rev Cell Biol. 1993;9:265–315. doi: 10.1146/annurev.cb.09.110193.001405. [DOI] [PubMed] [Google Scholar]
  62. Su L., Knipe D. M. Herpes simplex virus alpha protein ICP27 can inhibit or augment viral gene transactivation. Virology. 1989 Jun;170(2):496–504. doi: 10.1016/0042-6822(89)90441-8. [DOI] [PubMed] [Google Scholar]
  63. Séraphin B. Sm and Sm-like proteins belong to a large family: identification of proteins of the U6 as well as the U1, U2, U4 and U5 snRNPs. EMBO J. 1995 May 1;14(9):2089–2098. doi: 10.1002/j.1460-2075.1995.tb07200.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Tazi J., Kornstädt U., Rossi F., Jeanteur P., Cathala G., Brunel C., Lührmann R. Thiophosphorylation of U1-70K protein inhibits pre-mRNA splicing. Nature. 1993 May 20;363(6426):283–286. doi: 10.1038/363283a0. [DOI] [PubMed] [Google Scholar]
  65. Tian M., Maniatis T. A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA. Cell. 1993 Jul 16;74(1):105–114. doi: 10.1016/0092-8674(93)90298-5. [DOI] [PubMed] [Google Scholar]
  66. Vaughan P. J., Thibault K. J., Hardwicke M. A., Sandri-Goldin R. M. The herpes simplex virus immediate early protein ICP27 encodes a potential metal binding domain and binds zinc in vitro. Virology. 1992 Jul;189(1):377–384. doi: 10.1016/0042-6822(92)90720-a. [DOI] [PubMed] [Google Scholar]
  67. Wilcox K. W., Kohn A., Sklyanskaya E., Roizman B. Herpes simplex virus phosphoproteins. I. Phosphate cycles on and off some viral polypeptides and can alter their affinity for DNA. J Virol. 1980 Jan;33(1):167–182. doi: 10.1128/jvi.33.1.167-182.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Woppmann A., Patschinsky T., Bringmann P., Godt F., Lührmann R. Characterisation of human and murine snRNP proteins by two-dimensional gel electrophoresis and phosphopeptide analysis of U1-specific 70K protein variants. Nucleic Acids Res. 1990 Aug 11;18(15):4427–4438. doi: 10.1093/nar/18.15.4427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Woppmann A., Will C. L., Kornstädt U., Zuo P., Manley J. L., Lührmann R. Identification of an snRNP-associated kinase activity that phosphorylates arginine/serine rich domains typical of splicing factors. Nucleic Acids Res. 1993 Jun 25;21(12):2815–2822. doi: 10.1093/nar/21.12.2815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Wu J. Y., Maniatis T. Specific interactions between proteins implicated in splice site selection and regulated alternative splicing. Cell. 1993 Dec 17;75(6):1061–1070. doi: 10.1016/0092-8674(93)90316-i. [DOI] [PubMed] [Google Scholar]
  71. Zahler A. M., Lane W. S., Stolk J. A., Roth M. B. SR proteins: a conserved family of pre-mRNA splicing factors. Genes Dev. 1992 May;6(5):837–847. doi: 10.1101/gad.6.5.837. [DOI] [PubMed] [Google Scholar]
  72. Zahler A. M., Neugebauer K. M., Lane W. S., Roth M. B. Distinct functions of SR proteins in alternative pre-mRNA splicing. Science. 1993 Apr 9;260(5105):219–222. doi: 10.1126/science.8385799. [DOI] [PubMed] [Google Scholar]
  73. Zahler A. M., Neugebauer K. M., Stolk J. A., Roth M. B. Human SR proteins and isolation of a cDNA encoding SRp75. Mol Cell Biol. 1993 Jul;13(7):4023–4028. doi: 10.1128/mcb.13.7.4023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Zahler A. M., Roth M. B. Distinct functions of SR proteins in recruitment of U1 small nuclear ribonucleoprotein to alternative 5' splice sites. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2642–2646. doi: 10.1073/pnas.92.7.2642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Zamore P. D., Green M. R. Biochemical characterization of U2 snRNP auxiliary factor: an essential pre-mRNA splicing factor with a novel intranuclear distribution. EMBO J. 1991 Jan;10(1):207–214. doi: 10.1002/j.1460-2075.1991.tb07937.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Zamore P. D., Green M. R. Identification, purification, and biochemical characterization of U2 small nuclear ribonucleoprotein auxiliary factor. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9243–9247. doi: 10.1073/pnas.86.23.9243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. 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]
  78. Zeng C., He D., Berget S. M., Brinkley B. R. Nuclear-mitotic apparatus protein: a structural protein interface between the nucleoskeleton and RNA splicing. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1505–1509. doi: 10.1073/pnas.91.4.1505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Zhang G., Taneja K. L., Singer R. H., Green M. R. Localization of pre-mRNA splicing in mammalian nuclei. Nature. 1994 Dec 22;372(6508):809–812. doi: 10.1038/372809a0. [DOI] [PubMed] [Google Scholar]

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