Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1993 May;12(5):2119–2128. doi: 10.1002/j.1460-2075.1993.tb05860.x

Tat-dependent occlusion of the HIV poly(A) site.

C Weichs an der Glon 1, M Ashe 1, J Eggermont 1, N J Proudfoot 1
PMCID: PMC413433  PMID: 8491200

Abstract

Retroviruses must ensure that poly(A) signals in the 3' LTR are highly active, while identical signals in the 5' LTR are inactive (occluded). In the case of HIV-1, both promoter proximity in the 5' LTR and U3 sequences in the 3' LTR may contribute to this regulation. We have discovered a novel regulatory mechanism for poly(A) site occlusion in HIV-1. When transcription initiation from the HIV promoter is activated by Tat, the HIV poly(A) site is specifically occluded, while other poly(A) sites are unaffected by Tat. Nucleotide signals associated with this Tat effect are immediately adjacent to the AAUAAA sequence of the HIV-1 poly(A) signal. These data suggest that elongating RNA polymerase II, activated by Tat specifically occludes the HIV poly(A) site.

Full text

PDF

Images in this article

2121Image
on p.2121
2122Image
on p.2122
2124Image
on p.2124
2125Image
on p.2125

Selected References

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

  1. Adams S. E., Johnson I. D., Braddock M., Kingsman A. J., Kingsman S. M., Edwards R. M. Synthesis of a gene for the HIV transactivator protein TAT by a novel single stranded approach involving in vivo gap repair. Nucleic Acids Res. 1988 May 25;16(10):4287–4298. doi: 10.1093/nar/16.10.4287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ahmed Y. F., Gilmartin G. M., Hanly S. M., Nevins J. R., Greene W. C. The HTLV-I Rex response element mediates a novel form of mRNA polyadenylation. Cell. 1991 Feb 22;64(4):727–737. doi: 10.1016/0092-8674(91)90502-p. [DOI] [PubMed] [Google Scholar]
  3. Berkhout B., Silverman R. H., Jeang K. T. Tat trans-activates the human immunodeficiency virus through a nascent RNA target. Cell. 1989 Oct 20;59(2):273–282. doi: 10.1016/0092-8674(89)90289-4. [DOI] [PubMed] [Google Scholar]
  4. Brown P. H., Tiley L. S., Cullen B. R. Efficient polyadenylation within the human immunodeficiency virus type 1 long terminal repeat requires flanking U3-specific sequences. J Virol. 1991 Jun;65(6):3340–3343. doi: 10.1128/jvi.65.6.3340-3343.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cherrington J., Ganem D. Regulation of polyadenylation in human immunodeficiency virus (HIV): contributions of promoter proximity and upstream sequences. EMBO J. 1992 Apr;11(4):1513–1524. doi: 10.1002/j.1460-2075.1992.tb05196.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Connelly S., Manley J. L. A functional mRNA polyadenylation signal is required for transcription termination by RNA polymerase II. Genes Dev. 1988 Apr;2(4):440–452. doi: 10.1101/gad.2.4.440. [DOI] [PubMed] [Google Scholar]
  7. Cullen B. R. The HIV-1 Tat protein: an RNA sequence-specific processivity factor? Cell. 1990 Nov 16;63(4):655–657. doi: 10.1016/0092-8674(90)90129-3. [DOI] [PubMed] [Google Scholar]
  8. DeZazzo J. D., Kilpatrick J. E., Imperiale M. J. Involvement of long terminal repeat U3 sequences overlapping the transcription control region in human immunodeficiency virus type 1 mRNA 3' end formation. Mol Cell Biol. 1991 Mar;11(3):1624–1630. doi: 10.1128/mcb.11.3.1624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dingwall C., Ernberg I., Gait M. J., Green S. M., Heaphy S., Karn J., Lowe A. D., Singh M., Skinner M. A., Valerio R. Human immunodeficiency virus 1 tat protein binds trans-activation-responsive region (TAR) RNA in vitro. Proc Natl Acad Sci U S A. 1989 Sep;86(18):6925–6929. doi: 10.1073/pnas.86.18.6925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Enriquez-Harris P., Levitt N., Briggs D., Proudfoot N. J. A pause site for RNA polymerase II is associated with termination of transcription. EMBO J. 1991 Jul;10(7):1833–1842. doi: 10.1002/j.1460-2075.1991.tb07709.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feinberg M. B., Baltimore D., Frankel A. D. The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation. Proc Natl Acad Sci U S A. 1991 May 1;88(9):4045–4049. doi: 10.1073/pnas.88.9.4045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Frankel A. D. Activation of HIV transcription by Tat. Curr Opin Genet Dev. 1992 Apr;2(2):293–298. doi: 10.1016/s0959-437x(05)80287-4. [DOI] [PubMed] [Google Scholar]
  13. Gilmartin G. M., Fleming E. S., Oetjen J. Activation of HIV-1 pre-mRNA 3' processing in vitro requires both an upstream element and TAR. EMBO J. 1992 Dec;11(12):4419–4428. doi: 10.1002/j.1460-2075.1992.tb05542.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Grosveld G. C., de Boer E., Shewmaker C. K., Flavell R. A. DNA sequences necessary for transcription of the rabbit beta-globin gene in vivo. Nature. 1982 Jan 14;295(5845):120–126. doi: 10.1038/295120a0. [DOI] [PubMed] [Google Scholar]
  15. Hauber J., Perkins A., Heimer E. P., Cullen B. R. Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6364–6368. doi: 10.1073/pnas.84.18.6364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Higgs D. R., Goodbourn S. E., Lamb J., Clegg J. B., Weatherall D. J., Proudfoot N. J. Alpha-thalassaemia caused by a polyadenylation signal mutation. Nature. 1983 Nov 24;306(5941):398–400. doi: 10.1038/306398a0. [DOI] [PubMed] [Google Scholar]
  17. Iwasaki K., Temin H. M. Multiple sequence elements are involved in RNA 3' end formation in spleen necrosis virus. Gene Expr. 1992;2(1):7–18. [PMC free article] [PubMed] [Google Scholar]
  18. Iwasaki K., Temin H. M. The efficiency of RNA 3'-end formation is determined by the distance between the cap site and the poly(A) site in spleen necrosis virus. Genes Dev. 1990 Dec;4(12B):2299–2307. doi: 10.1101/gad.4.12b.2299. [DOI] [PubMed] [Google Scholar]
  19. Jackson R. J., Standart N. Do the poly(A) tail and 3' untranslated region control mRNA translation? Cell. 1990 Jul 13;62(1):15–24. doi: 10.1016/0092-8674(90)90235-7. [DOI] [PubMed] [Google Scholar]
  20. Johnson M. R., Norman C., Reeve M. A., Scully J., Proudfoot N. J. Tripartite sequences within and 3' to the sea urchin H2A histone gene display properties associated with a transcriptional termination process. Mol Cell Biol. 1986 Nov;6(11):4008–4018. doi: 10.1128/mcb.6.11.4008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jones K. A. HIV trans-activation and transcription control mechanisms. New Biol. 1989 Nov;1(2):127–135. [PubMed] [Google Scholar]
  22. Kao S. Y., Calman A. F., Luciw P. A., Peterlin B. M. Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product. Nature. 1987 Dec 3;330(6147):489–493. doi: 10.1038/330489a0. [DOI] [PubMed] [Google Scholar]
  23. Kato H., Sumimoto H., Pognonec P., Chen C. H., Rosen C. A., Roeder R. G. HIV-1 Tat acts as a processivity factor in vitro in conjunction with cellular elongation factors. Genes Dev. 1992 Apr;6(4):655–666. doi: 10.1101/gad.6.4.655. [DOI] [PubMed] [Google Scholar]
  24. Laspia M. F., Rice A. P., Mathews M. B. HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation. Cell. 1989 Oct 20;59(2):283–292. doi: 10.1016/0092-8674(89)90290-0. [DOI] [PubMed] [Google Scholar]
  25. Laspia M. F., Rice A. P., Mathews M. B. Synergy between HIV-1 Tat and adenovirus E1A is principally due to stabilization of transcriptional elongation. Genes Dev. 1990 Dec;4(12B):2397–2408. doi: 10.1101/gad.4.12b.2397. [DOI] [PubMed] [Google Scholar]
  26. Levitt N., Briggs D., Gil A., Proudfoot N. J. Definition of an efficient synthetic poly(A) site. Genes Dev. 1989 Jul;3(7):1019–1025. doi: 10.1101/gad.3.7.1019. [DOI] [PubMed] [Google Scholar]
  27. Logan J., Falck-Pedersen E., Darnell J. E., Jr, Shenk T. A poly(A) addition site and a downstream termination region are required for efficient cessation of transcription by RNA polymerase II in the mouse beta maj-globin gene. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8306–8310. doi: 10.1073/pnas.84.23.8306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lusky M., Botchan M. Inhibition of SV40 replication in simian cells by specific pBR322 DNA sequences. Nature. 1981 Sep 3;293(5827):79–81. doi: 10.1038/293079a0. [DOI] [PubMed] [Google Scholar]
  29. Marciniak R. A., Sharp P. A. HIV-1 Tat protein promotes formation of more-processive elongation complexes. EMBO J. 1991 Dec;10(13):4189–4196. doi: 10.1002/j.1460-2075.1991.tb04997.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mellon P., Parker V., Gluzman Y., Maniatis T. Identification of DNA sequences required for transcription of the human alpha 1-globin gene in a new SV40 host-vector system. Cell. 1981 Dec;27(2 Pt 1):279–288. doi: 10.1016/0092-8674(81)90411-6. [DOI] [PubMed] [Google Scholar]
  31. Proudfoot N. J., Lee B. A., Monks J. Multiple SP1 binding sites confer enhancer-independent, replication-activated transcription of HIV-1 and globin gene promoters. New Biol. 1992 Apr;4(4):369–381. [PubMed] [Google Scholar]
  32. Proudfoot N. Poly(A) signals. Cell. 1991 Feb 22;64(4):671–674. doi: 10.1016/0092-8674(91)90495-k. [DOI] [PubMed] [Google Scholar]
  33. Sharp P. A., Marciniak R. A. HIV TAR: an RNA enhancer? Cell. 1989 Oct 20;59(2):229–230. doi: 10.1016/0092-8674(89)90279-1. [DOI] [PubMed] [Google Scholar]
  34. Southgate C. D., Green M. R. The HIV-1 Tat protein activates transcription from an upstream DNA-binding site: implications for Tat function. Genes Dev. 1991 Dec;5(12B):2496–2507. doi: 10.1101/gad.5.12b.2496. [DOI] [PubMed] [Google Scholar]
  35. Valsamakis A., Schek N., Alwine J. C. Elements upstream of the AAUAAA within the human immunodeficiency virus polyadenylation signal are required for efficient polyadenylation in vitro. Mol Cell Biol. 1992 Sep;12(9):3699–3705. doi: 10.1128/mcb.12.9.3699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Valsamakis A., Zeichner S., Carswell S., Alwine J. C. The human immunodeficiency virus type 1 polyadenylylation signal: a 3' long terminal repeat element upstream of the AAUAAA necessary for efficient polyadenylylation. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2108–2112. doi: 10.1073/pnas.88.6.2108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Weichs an der Glon C., Monks J., Proudfoot N. J. Occlusion of the HIV poly(A) site. Genes Dev. 1991 Feb;5(2):244–253. doi: 10.1101/gad.5.2.244. [DOI] [PubMed] [Google Scholar]
  38. Whitelaw E., Proudfoot N. Alpha-thalassaemia caused by a poly(A) site mutation reveals that transcriptional termination is linked to 3' end processing in the human alpha 2 globin gene. EMBO J. 1986 Nov;5(11):2915–2922. doi: 10.1002/j.1460-2075.1986.tb04587.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES