Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1994 Mar;68(3):1475–1485. doi: 10.1128/jvi.68.3.1475-1485.1994

Subcellular distribution of human immunodeficiency virus type 1 Rev and colocalization of Rev with RNA splicing factors in a speckled pattern in the nucleoplasm.

K H Kalland 1, A M Szilvay 1, E Langhoff 1, G Haukenes 1
PMCID: PMC236603  PMID: 8107211

Abstract

The human immunodeficiency virus type 1 (HIV-1) Rev (regulator of virion protein expression) protein exemplifies a new type of posttranscriptional regulation. One main function of Rev is to increase the cytoplasmic expression of unspliced and incompletely spliced retroviral mRNAs from which viral structural proteins are made. In that way, Rev is essential in order to complete the retroviral life cycle. The biology of Rev in the host cell has remained elusive. In this study, a complex distribution of Rev in single cells was found. Rev was found in the cytoplasm, in a perinuclear zone, in the nucleoplasm, and in the nucleoli. In the nucleoplasm, Rev colocalized in a speckled pattern with host cell factors known to assemble on nascent transcripts. Those factors are involved in the processing of heterogeneous RNA to spliced mRNA in the nucleoplasm of all cells. The distribution of Rev was dependent only on Rev and host cell interactions, since neither the Rev target RNA nor other HIV proteins were expressed in the cells. Rev was found in the same subcellular compartments of cells treated for extended periods with cycloheximide, an inhibitor of protein synthesis. This finding implies that Rev shuttles continuously between cytoplasmic and nucleoplasmic compartments. The results suggest a potential role for Rev both in the RNA-splicing process and in the nucleocytoplasmic transport of Rev-dependent HIV mRNA.

Full text

PDF
1476

Images in this article

1477Image
on p.1477
1478Image
on p.1478
1480Image
on p.1480
1481Image
on p.1481

Selected References

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

  1. Arrigo S. J., Chen I. S. Rev is necessary for translation but not cytoplasmic accumulation of HIV-1 vif, vpr, and env/vpu 2 RNAs. Genes Dev. 1991 May;5(5):808–819. doi: 10.1101/gad.5.5.808. [DOI] [PubMed] [Google Scholar]
  2. Arrigo S. J., Heaphy S., Haines J. K. In vivo binding of wild-type and mutant human immunodeficiency virus type 1 Rev proteins: implications for function. J Virol. 1992 Sep;66(9):5569–5575. doi: 10.1128/jvi.66.9.5569-5575.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ascoli C. A., Maul G. G. Identification of a novel nuclear domain. J Cell Biol. 1991 Mar;112(5):785–795. doi: 10.1083/jcb.112.5.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bachmann M., Mayet W. J., Schröder H. C., Pfeifer K., Meyer zum Büschenfelde K. H., Müller W. E. Association of La and Ro antigens with intracellular structures in HEp-2 carcinoma cells. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7770–7774. doi: 10.1073/pnas.83.20.7770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bochnig P., Reuter R., Bringmann P., Lührmann R. A monoclonal antibody against 2,2,7-trimethylguanosine that reacts with intact, class U, small nuclear ribonucleoproteins as well as with 7-methylguanosine-capped RNAs. Eur J Biochem. 1987 Oct 15;168(2):461–467. doi: 10.1111/j.1432-1033.1987.tb13439.x. [DOI] [PubMed] [Google Scholar]
  6. Borer R. A., Lehner C. F., Eppenberger H. M., Nigg E. A. Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell. 1989 Feb 10;56(3):379–390. doi: 10.1016/0092-8674(89)90241-9. [DOI] [PubMed] [Google Scholar]
  7. Carmo-Fonseca M., Pepperkok R., Sproat B. S., Ansorge W., Swanson M. S., Lamond A. I. In vivo detection of snRNP-rich organelles in the nuclei of mammalian cells. EMBO J. 1991 Jul;10(7):1863–1873. doi: 10.1002/j.1460-2075.1991.tb07712.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carter K. C., Taneja K. L., Lawrence J. B. Discrete nuclear domains of poly(A) RNA and their relationship to the functional organization of the nucleus. J Cell Biol. 1991 Dec;115(5):1191–1202. doi: 10.1083/jcb.115.5.1191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang D. D., Sharp P. A. Regulation by HIV Rev depends upon recognition of splice sites. Cell. 1989 Dec 1;59(5):789–795. doi: 10.1016/0092-8674(89)90602-8. [DOI] [PubMed] [Google Scholar]
  10. Chida K., Vogt P. K. Nuclear translocation of viral Jun but not of cellular Jun is cell cycle dependent. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4290–4294. doi: 10.1073/pnas.89.10.4290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Choi Y. D., Dreyfuss G. Monoclonal antibody characterization of the C proteins of heterogeneous nuclear ribonucleoprotein complexes in vertebrate cells. J Cell Biol. 1984 Dec;99(6):1997–1204. doi: 10.1083/jcb.99.6.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cochrane A. W., Jones K. S., Beidas S., Dillon P. J., Skalka A. M., Rosen C. A. Identification and characterization of intragenic sequences which repress human immunodeficiency virus structural gene expression. J Virol. 1991 Oct;65(10):5305–5313. doi: 10.1128/jvi.65.10.5305-5313.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cochrane A. W., Perkins A., Rosen C. A. Identification of sequences important in the nucleolar localization of human immunodeficiency virus Rev: relevance of nucleolar localization to function. J Virol. 1990 Feb;64(2):881–885. doi: 10.1128/jvi.64.2.881-885.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cullen B. R., Hauber J., Campbell K., Sodroski J. G., Haseltine W. A., Rosen C. A. Subcellular localization of the human immunodeficiency virus trans-acting art gene product. J Virol. 1988 Jul;62(7):2498–2501. doi: 10.1128/jvi.62.7.2498-2501.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cullen B. R. Mechanism of action of regulatory proteins encoded by complex retroviruses. Microbiol Rev. 1992 Sep;56(3):375–394. doi: 10.1128/mr.56.3.375-394.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. D'Agostino D. M., Felber B. K., Harrison J. E., Pavlakis G. N. The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag/pol and vpu/env mRNAs. Mol Cell Biol. 1992 Mar;12(3):1375–1386. doi: 10.1128/mcb.12.3.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Daly T. J., Cook K. S., Gray G. S., Maione T. E., Rusche J. R. Specific binding of HIV-1 recombinant Rev protein to the Rev-responsive element in vitro. Nature. 1989 Dec 14;342(6251):816–819. doi: 10.1038/342816a0. [DOI] [PubMed] [Google Scholar]
  18. Davis L. I., Blobel G. Identification and characterization of a nuclear pore complex protein. Cell. 1986 Jun 6;45(5):699–709. doi: 10.1016/0092-8674(86)90784-1. [DOI] [PubMed] [Google Scholar]
  19. Dayton E. T., Powell D. M., Dayton A. I. Functional analysis of CAR, the target sequence for the Rev protein of HIV-1. Science. 1989 Dec 22;246(4937):1625–1629. doi: 10.1126/science.2688093. [DOI] [PubMed] [Google Scholar]
  20. Emerman M., Vazeux R., Peden K. The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization. Cell. 1989 Jun 30;57(7):1155–1165. doi: 10.1016/0092-8674(89)90053-6. [DOI] [PubMed] [Google Scholar]
  21. Fakan S., Leser G., Martin T. E. Ultrastructural distribution of nuclear ribonucleoproteins as visualized by immunocytochemistry on thin sections. J Cell Biol. 1984 Jan;98(1):358–363. doi: 10.1083/jcb.98.1.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Fankhauser C., Izaurralde E., Adachi Y., Wingfield P., Laemmli U. K. Specific complex of human immunodeficiency virus type 1 rev and nucleolar B23 proteins: dissociation by the Rev response element. Mol Cell Biol. 1991 May;11(5):2567–2575. doi: 10.1128/mcb.11.5.2567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Feinberg M. B., Jarrett R. F., Aldovini A., Gallo R. C., Wong-Staal F. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell. 1986 Sep 12;46(6):807–817. doi: 10.1016/0092-8674(86)90062-0. [DOI] [PubMed] [Google Scholar]
  24. Felber B. K., Hadzopoulou-Cladaras M., Cladaras C., Copeland T., Pavlakis G. N. rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495–1499. doi: 10.1073/pnas.86.5.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Freeman J. W., Chatterjee A., Ross B. E., Busch H. Epitope distribution and immunochemical characterization of nucleolar phosphoprotein C23 using ten monoclonal antibodies. Mol Cell Biochem. 1985 Sep;68(1):87–96. doi: 10.1007/BF00219392. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. 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]
  29. Hammarskjöld M. L., Heimer J., Hammarskjöld B., Sangwan I., Albert L., Rekosh D. Regulation of human immunodeficiency virus env expression by the rev gene product. J Virol. 1989 May;63(5):1959–1966. doi: 10.1128/jvi.63.5.1959-1966.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Heaphy S., Dingwall C., Ernberg I., Gait M. J., Green S. M., Karn J., Lowe A. D., Singh M., Skinner M. A. HIV-1 regulator of virion expression (Rev) protein binds to an RNA stem-loop structure located within the Rev response element region. Cell. 1990 Feb 23;60(4):685–693. doi: 10.1016/0092-8674(90)90671-z. [DOI] [PubMed] [Google Scholar]
  31. Hope T. J., McDonald D., Huang X. J., Low J., Parslow T. G. Mutational analysis of the human immunodeficiency virus type 1 Rev transactivator: essential residues near the amino terminus. J Virol. 1990 Nov;64(11):5360–5366. doi: 10.1128/jvi.64.11.5360-5366.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Huang S., Spector D. L. Nascent pre-mRNA transcripts are associated with nuclear regions enriched in splicing factors. Genes Dev. 1991 Dec;5(12A):2288–2302. doi: 10.1101/gad.5.12a.2288. [DOI] [PubMed] [Google Scholar]
  33. Huang X. J., Hope T. J., Bond B. L., McDonald D., Grahl K., Parslow T. G. Minimal Rev-response element for type 1 human immunodeficiency virus. J Virol. 1991 Apr;65(4):2131–2134. doi: 10.1128/jvi.65.4.2131-2134.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Jackson D. A., Hassan A. B., Errington R. J., Cook P. R. Visualization of focal sites of transcription within human nuclei. EMBO J. 1993 Mar;12(3):1059–1065. doi: 10.1002/j.1460-2075.1993.tb05747.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Kalland K. H., Langhoff E., Bos H. J., Göttlinger H., Haseltine W. A. Rex-dependent nucleolar accumulation of HTLV-I mRNAs. New Biol. 1991 Apr;3(4):389–397. [PubMed] [Google Scholar]
  37. Kiyokawa T., Seiki M., Iwashita S., Imagawa K., Shimizu F., Yoshida M. p27x-III and p21x-III, proteins encoded by the pX sequence of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8359–8363. doi: 10.1073/pnas.82.24.8359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kjems J., Brown M., Chang D. D., Sharp P. A. Structural analysis of the interaction between the human immunodeficiency virus Rev protein and the Rev response element. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):683–687. doi: 10.1073/pnas.88.3.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Kjems J., Sharp P. A. The basic domain of Rev from human immunodeficiency virus type 1 specifically blocks the entry of U4/U6.U5 small nuclear ribonucleoprotein in spliceosome assembly. J Virol. 1993 Aug;67(8):4769–4776. doi: 10.1128/jvi.67.8.4769-4776.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Lu X. B., Heimer J., Rekosh D., Hammarskjöld M. L. U1 small nuclear RNA plays a direct role in the formation of a rev-regulated human immunodeficiency virus env mRNA that remains unspliced. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7598–7602. doi: 10.1073/pnas.87.19.7598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Maldarelli F., Martin M. A., Strebel K. Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation. J Virol. 1991 Nov;65(11):5732–5743. doi: 10.1128/jvi.65.11.5732-5743.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Malim M. H., Böhnlein S., Hauber J., Cullen B. R. Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function. Cell. 1989 Jul 14;58(1):205–214. doi: 10.1016/0092-8674(89)90416-9. [DOI] [PubMed] [Google Scholar]
  44. Malim M. H., Fenrick R., Ballard D. W., Hauber J., Böhnlein E., Cullen B. R. Functional characterization of a complex protein-DNA-binding domain located within the human immunodeficiency virus type 1 long terminal repeat leader region. J Virol. 1989 Aug;63(8):3213–3219. doi: 10.1128/jvi.63.8.3213-3219.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Malim M. H., Hauber J., Fenrick R., Cullen B. R. Immunodeficiency virus rev trans-activator modulates the expression of the viral regulatory genes. Nature. 1988 Sep 8;335(6186):181–183. doi: 10.1038/335181a0. [DOI] [PubMed] [Google Scholar]
  46. Malim M. H., Hauber J., Le S. Y., Maizel J. V., Cullen B. R. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989 Mar 16;338(6212):254–257. doi: 10.1038/338254a0. [DOI] [PubMed] [Google Scholar]
  47. Malim M. H., McCarn D. F., Tiley L. S., Cullen B. R. Mutational definition of the human immunodeficiency virus type 1 Rev activation domain. J Virol. 1991 Aug;65(8):4248–4254. doi: 10.1128/jvi.65.8.4248-4254.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Malim M. H., Tiley L. S., McCarn D. F., Rusche J. R., Hauber J., Cullen B. R. HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence. Cell. 1990 Feb 23;60(4):675–683. doi: 10.1016/0092-8674(90)90670-a. [DOI] [PubMed] [Google Scholar]
  49. Mermer B., Felber B. K., Campbell M., Pavlakis G. N. Identification of trans-dominant HIV-1 rev protein mutants by direct transfer of bacterially produced proteins into human cells. Nucleic Acids Res. 1990 Apr 25;18(8):2037–2044. doi: 10.1093/nar/18.8.2037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Ochs R., Lischwe M., O'Leary P., Busch H. Localization of nucleolar phosphoproteins B23 and C23 during mitosis. Exp Cell Res. 1983 Jun;146(1):139–149. doi: 10.1016/0014-4827(83)90332-4. [DOI] [PubMed] [Google Scholar]
  51. Olsen H. S., Cochrane A. W., Dillon P. J., Nalin C. M., Rosen C. A. Interaction of the human immunodeficiency virus type 1 Rev protein with a structured region in env mRNA is dependent on multimer formation mediated through a basic stretch of amino acids. Genes Dev. 1990 Aug;4(8):1357–1364. doi: 10.1101/gad.4.8.1357. [DOI] [PubMed] [Google Scholar]
  52. Olsen H. S., Nelbock P., Cochrane A. W., Rosen C. A. Secondary structure is the major determinant for interaction of HIV rev protein with RNA. Science. 1990 Feb 16;247(4944):845–848. doi: 10.1126/science.2406903. [DOI] [PubMed] [Google Scholar]
  53. Pines J., Hunter T. Human cell division: the involvement of cyclins A and B1, and multiple cdc2s. Cold Spring Harb Symp Quant Biol. 1991;56:449–463. doi: 10.1101/sqb.1991.056.01.052. [DOI] [PubMed] [Google Scholar]
  54. Piñol-Roma S., Dreyfuss G. Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature. 1992 Feb 20;355(6362):730–732. doi: 10.1038/355730a0. [DOI] [PubMed] [Google Scholar]
  55. Piñol-Roma S., Swanson M. S., Gall J. G., Dreyfuss G. A novel heterogeneous nuclear RNP protein with a unique distribution on nascent transcripts. J Cell Biol. 1989 Dec;109(6 Pt 1):2575–2587. doi: 10.1083/jcb.109.6.2575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Raska I., Andrade L. E., Ochs R. L., Chan E. K., Chang C. M., Roos G., Tan E. M. Immunological and ultrastructural studies of the nuclear coiled body with autoimmune antibodies. Exp Cell Res. 1991 Jul;195(1):27–37. doi: 10.1016/0014-4827(91)90496-h. [DOI] [PubMed] [Google Scholar]
  57. Reuter R., Appel B., Bringmann P., Rinke J., Lührmann R. 5'-Terminal caps of snRNAs are reactive with antibodies specific for 2,2,7-trimethylguanosine in whole cells and nuclear matrices. Double-label immunofluorescent studies with anti-m3G antibodies and with anti-RNP and anti-Sm autoantibodies. Exp Cell Res. 1984 Oct;154(2):548–560. doi: 10.1016/0014-4827(84)90179-4. [DOI] [PubMed] [Google Scholar]
  58. Riabowol K. T., Fink J. S., Gilman M. Z., Walsh D. A., Goodman R. H., Feramisco J. R. The catalytic subunit of cAMP-dependent protein kinase induces expression of genes containing cAMP-responsive enhancer elements. Nature. 1988 Nov 3;336(6194):83–86. doi: 10.1038/336083a0. [DOI] [PubMed] [Google Scholar]
  59. Richardson W. D., Mills A. D., Dilworth S. M., Laskey R. A., Dingwall C. Nuclear protein migration involves two steps: rapid binding at the nuclear envelope followed by slower translocation through nuclear pores. Cell. 1988 Mar 11;52(5):655–664. doi: 10.1016/0092-8674(88)90403-5. [DOI] [PubMed] [Google Scholar]
  60. Rosen C. A., Terwilliger E., Dayton A., Sodroski J. G., Haseltine W. A. Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2071–2075. doi: 10.1073/pnas.85.7.2071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Sadaie M. R., Benter T., Wong-Staal F. Site-directed mutagenesis of two trans-regulatory genes (tat-III,trs) of HIV-1. Science. 1988 Feb 19;239(4842):910–913. doi: 10.1126/science.3277284. [DOI] [PubMed] [Google Scholar]
  62. Saunders W. S., Cooke C. A., Earnshaw W. C. Compartmentalization within the nucleus: discovery of a novel subnuclear region. J Cell Biol. 1991 Nov;115(4):919–931. doi: 10.1083/jcb.115.4.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Schwartz S., Felber B. K., Benko D. M., Fenyö E. M., Pavlakis G. N. Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1. J Virol. 1990 Jun;64(6):2519–2529. doi: 10.1128/jvi.64.6.2519-2529.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Schwartz S., Felber B. K., Pavlakis G. N. Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein. J Virol. 1992 Jan;66(1):150–159. doi: 10.1128/jvi.66.1.150-159.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Snow C. M., Senior A., Gerace L. Monoclonal antibodies identify a group of nuclear pore complex glycoproteins. J Cell Biol. 1987 May;104(5):1143–1156. doi: 10.1083/jcb.104.5.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Sodroski J., Goh W. C., Rosen C., Dayton A., Terwilliger E., Haseltine W. A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature. 1986 May 22;321(6068):412–417. doi: 10.1038/321412a0. [DOI] [PubMed] [Google Scholar]
  67. 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]
  68. Spector D. L., Schrier W. H., Busch H. Immunoelectron microscopic localization of snRNPs. Biol Cell. 1983;49(1):1–10. doi: 10.1111/j.1768-322x.1984.tb00215.x. [DOI] [PubMed] [Google Scholar]
  69. Terwilliger E., Burghoff R., Sia R., Sodroski J., Haseltine W., Rosen C. The art gene product of human immunodeficiency virus is required for replication. J Virol. 1988 Feb;62(2):655–658. doi: 10.1128/jvi.62.2.655-658.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Venkatesh L. K., Chinnadurai G. Mutants in a conserved region near the carboxy-terminus of HIV-1 Rev identify functionally important residues and exhibit a dominant negative phenotype. Virology. 1990 Sep;178(1):327–330. doi: 10.1016/0042-6822(90)90414-m. [DOI] [PubMed] [Google Scholar]
  71. Wang J., Cao L. G., Wang Y. L., Pederson T. Localization of pre-messenger RNA at discrete nuclear sites. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7391–7395. doi: 10.1073/pnas.88.16.7391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Xing Y., Johnson C. V., Dobner P. R., Lawrence J. B. Higher level organization of individual gene transcription and RNA splicing. Science. 1993 Feb 26;259(5099):1326–1330. doi: 10.1126/science.8446901. [DOI] [PubMed] [Google Scholar]
  73. 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]
  74. Zapp M. L., Green M. R. Sequence-specific RNA binding by the HIV-1 Rev protein. Nature. 1989 Dec 7;342(6250):714–716. doi: 10.1038/342714a0. [DOI] [PubMed] [Google Scholar]
  75. Zhang M., Zamore P. D., Carmo-Fonseca M., Lamond A. I., Green M. R. Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8769–8773. doi: 10.1073/pnas.89.18.8769. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES