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. 1996 Sep;70(9):6442–6445. doi: 10.1128/jvi.70.9.6442-6445.1996

The human T-cell leukemia virus type 1 posttranscriptional trans-activator Rex contains a nuclear export signal.

D Palmeri 1, M H Malim 1
PMCID: PMC190676  PMID: 8709278

Abstract

The Rex protein of human T-cell leukemia virus type 1 is required for the nuclear export of unspliced viral mRNA and, therefore, for virus replication. In this manuscript, we demonstrate that Rex shuttles between the nucleus and the cytoplasm and that its activation domain constitutes a nuclear export signal that specifies efficient transport to the cytoplasm. These findings are consistent with a model for Rex-mediated trans-activation in which Rex-viral mRNA complexes are targeted for nuclear export by the direct action of the activation domain.

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Selected References

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  1. Ballaun C., Farrington G. K., Dobrovnik M., Rusche J., Hauber J., Böhnlein E. Functional analysis of human T-cell leukemia virus type I rex-response element: direct RNA binding of Rex protein correlates with in vivo activity. J Virol. 1991 Aug;65(8):4408–4413. doi: 10.1128/jvi.65.8.4408-4413.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bogerd H. P., Fridell R. A., Madore S., Cullen B. R. Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins. Cell. 1995 Aug 11;82(3):485–494. doi: 10.1016/0092-8674(95)90437-9. [DOI] [PubMed] [Google Scholar]
  3. Bogerd H. P., Huckaby G. L., Ahmed Y. F., Hanly S. M., Greene W. C. The type I human T-cell leukemia virus (HTLV-I) Rex trans-activator binds directly to the HTLV-I Rex and the type 1 human immunodeficiency virus Rev RNA response elements. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5704–5708. doi: 10.1073/pnas.88.13.5704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Böhnlein S., Pirker F. P., Hofer L., Zimmermann K., Bachmayer H., Böhnlein E., Hauber J. Transdominant repressors for human T-cell leukemia virus type I rex and human immunodeficiency virus type 1 rev function. J Virol. 1991 Jan;65(1):81–88. doi: 10.1128/jvi.65.1.81-88.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. 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]
  8. Fischer U., Huber J., Boelens W. C., Mattaj I. W., Lührmann R. The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell. 1995 Aug 11;82(3):475–483. doi: 10.1016/0092-8674(95)90436-0. [DOI] [PubMed] [Google Scholar]
  9. Fritz C. C., Zapp M. L., Green M. R. A human nucleoporin-like protein that specifically interacts with HIV Rev. Nature. 1995 Aug 10;376(6540):530–533. doi: 10.1038/376530a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Hanly S. M., Rimsky L. T., Malim M. H., Kim J. H., Hauber J., Duc Dodon M., Le S. Y., Maizel J. V., Cullen B. R., Greene W. C. Comparative analysis of the HTLV-I Rex and HIV-1 Rev trans-regulatory proteins and their RNA response elements. Genes Dev. 1989 Oct;3(10):1534–1544. doi: 10.1101/gad.3.10.1534. [DOI] [PubMed] [Google Scholar]
  12. Hidaka M., Inoue J., Yoshida M., Seiki M. Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins. EMBO J. 1988 Feb;7(2):519–523. doi: 10.1002/j.1460-2075.1988.tb02840.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hope T. J., Bond B. L., McDonald D., Klein N. P., Parslow T. G. Effector domains of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex are functionally interchangeable and share an essential peptide motif. J Virol. 1991 Nov;65(11):6001–6007. doi: 10.1128/jvi.65.11.6001-6007.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Inoue J., Yoshida M., Seiki M. Transcriptional (p40x) and post-transcriptional (p27x-III) regulators are required for the expression and replication of human T-cell leukemia virus type I genes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3653–3657. doi: 10.1073/pnas.84.11.3653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kalland K. H., Szilvay A. M., Brokstad K. A., Saetrevik W., Haukenes G. The human immunodeficiency virus type 1 Rev protein shuttles between the cytoplasm and nuclear compartments. Mol Cell Biol. 1994 Nov;14(11):7436–7444. doi: 10.1128/mcb.14.11.7436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Kiyomasu T., Miyazawa T., Furuya T., Shibata R., Sakai H., Sakuragi J., Fukasawa M., Maki N., Hasegawa A., Mikami T. Identification of feline immunodeficiency virus rev gene activity. J Virol. 1991 Aug;65(8):4539–4542. doi: 10.1128/jvi.65.8.4539-4542.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Malim M. H., Böhnlein S., Fenrick R., Le S. Y., Maizel J. V., Cullen B. R. Functional comparison of the Rev trans-activators encoded by different primate immunodeficiency virus species. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8222–8226. doi: 10.1073/pnas.86.21.8222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Malim M. H., Cullen B. R. Rev and the fate of pre-mRNA in the nucleus: implications for the regulation of RNA processing in eukaryotes. Mol Cell Biol. 1993 Oct;13(10):6180–6189. doi: 10.1128/mcb.13.10.6180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Mancuso V. A., Hope T. J., Zhu L., Derse D., Phillips T., Parslow T. G. Posttranscriptional effector domains in the Rev proteins of feline immunodeficiency virus and equine infectious anemia virus. J Virol. 1994 Mar;68(3):1998–2001. doi: 10.1128/jvi.68.3.1998-2001.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Meyer B. E., Malim M. H. The HIV-1 Rev trans-activator shuttles between the nucleus and the cytoplasm. Genes Dev. 1994 Jul 1;8(13):1538–1547. doi: 10.1101/gad.8.13.1538. [DOI] [PubMed] [Google Scholar]
  24. Meyer B. E., Meinkoth J. L., Malim M. H. Nuclear transport of human immunodeficiency virus type 1, visna virus, and equine infectious anemia virus Rev proteins: identification of a family of transferable nuclear export signals. J Virol. 1996 Apr;70(4):2350–2359. doi: 10.1128/jvi.70.4.2350-2359.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Richard N., Iacampo S., Cochrane A. HIV-1 Rev is capable of shuttling between the nucleus and cytoplasm. Virology. 1994 Oct;204(1):123–131. doi: 10.1006/viro.1994.1516. [DOI] [PubMed] [Google Scholar]
  28. Rimsky L., Dodon M. D., Dixon E. P., Greene W. C. Trans-dominant inactivation of HTLV-I and HIV-1 gene expression by mutation of the HTLV-I Rex transactivator. Nature. 1989 Oct 5;341(6241):453–456. doi: 10.1038/341453a0. [DOI] [PubMed] [Google Scholar]
  29. Ruhl M., Himmelspach M., Bahr G. M., Hammerschmid F., Jaksche H., Wolff B., Aschauer H., Farrington G. K., Probst H., Bevec D. Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activation. J Cell Biol. 1993 Dec;123(6 Pt 1):1309–1320. doi: 10.1083/jcb.123.6.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sakai H., Shibata R., Miura T., Hayami M., Ogawa K., Kiyomasu T., Ishimoto A., Adachi A. Complementation of the rev gene mutation among human and simian lentiviruses. J Virol. 1990 May;64(5):2202–2207. doi: 10.1128/jvi.64.5.2202-2207.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Siomi H., Shida H., Nam S. H., Nosaka T., Maki M., Hatanaka M. Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing. Cell. 1988 Oct 21;55(2):197–209. doi: 10.1016/0092-8674(88)90043-8. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Stauber R., Gaitanaris G. A., Pavlakis G. N. Analysis of trafficking of Rev and transdominant Rev proteins in living cells using green fluorescent protein fusions: transdominant Rev blocks the export of Rev from the nucleus to the cytoplasm. Virology. 1995 Nov 10;213(2):439–449. doi: 10.1006/viro.1995.0016. [DOI] [PubMed] [Google Scholar]
  34. Stutz F., Neville M., Rosbash M. Identification of a novel nuclear pore-associated protein as a functional target of the HIV-1 Rev protein in yeast. Cell. 1995 Aug 11;82(3):495–506. doi: 10.1016/0092-8674(95)90438-7. [DOI] [PubMed] [Google Scholar]
  35. Tiley L. S., Brown P. H., Le S. Y., Maizel J. V., Clements J. E., Cullen B. R. Visna virus encodes a post-transcriptional regulator of viral structural gene expression. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7497–7501. doi: 10.1073/pnas.87.19.7497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Toohey K. L., Haase A. T. The rev gene of visna virus is required for productive infection. Virology. 1994 Apr;200(1):276–280. doi: 10.1006/viro.1994.1186. [DOI] [PubMed] [Google Scholar]
  37. Unge T., Solomin L., Mellini M., Derse D., Felber B. K., Pavlakis G. N. The Rex regulatory protein of human T-cell lymphotropic virus type I binds specifically to its target site within the viral RNA. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7145–7149. doi: 10.1073/pnas.88.16.7145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Weichselbraun I., Farrington G. K., Rusche J. R., Böhnlein E., Hauber J. Definition of the human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex protein activation domain by functional exchange. J Virol. 1992 Apr;66(4):2583–2587. doi: 10.1128/jvi.66.4.2583-2587.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wen W., Meinkoth J. L., Tsien R. Y., Taylor S. S. Identification of a signal for rapid export of proteins from the nucleus. Cell. 1995 Aug 11;82(3):463–473. doi: 10.1016/0092-8674(95)90435-2. [DOI] [PubMed] [Google Scholar]

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