Abstract
The human immunodeficiency virus type 1 promoter generates two types of RNA molecules, full-length transcripts and short transcripts. Synthesis of the short transcripts depends on the inducer of short transcripts (IST), an element located downstream of the start site. In the presence of the viral activator Tat, the synthesis of full-length transcripts is up-regulated while that of short transcripts is down-regulated. Full-length and short transcripts are probably generated by different types of transcription complexes. The first is IST independent, capable of efficient elongation, and up-regulated by Tat. The second is IST dependent, incapable of efficient elongation, and down-regulated by Tat. We have used an in vivo assay to assess the role of TBP in human immunodeficiency virus type I transcription and to test the effect of mutations in TBP on synthesis of full-length and short transcripts. We find that TBP bound to the TATA box is required for the synthesis of short and full-length transcripts as well as for Tat activation and that both yeast TBP and the carboxy-terminal domain of human TBP can replace full-length human TBP for these processes. Mutations in TBP affect the synthesis of short and full-length transcripts as well as Tat activation similarly, and these effects correlate with the previously described effects of these mutations on binding of TBP to the TBP-associated factor TAFII250 in vitro. Together, these results suggest that if short and full-length transcripts are generated by variant transcription complexes, these complexes use TBP similarly, probably as part of the TFIID complex.
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- Berkhout B., Jeang K. T. Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat. J Virol. 1992 Jan;66(1):139–149. doi: 10.1128/jvi.66.1.139-149.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carey M., Kakidani H., Leatherwood J., Mostashari F., Ptashne M. An amino-terminal fragment of GAL4 binds DNA as a dimer. J Mol Biol. 1989 Oct 5;209(3):423–432. doi: 10.1016/0022-2836(89)90007-7. [DOI] [PubMed] [Google Scholar]
- Chen J. L., Attardi L. D., Verrijzer C. P., Yokomori K., Tjian R. Assembly of recombinant TFIID reveals differential coactivator requirements for distinct transcriptional activators. Cell. 1994 Oct 7;79(1):93–105. doi: 10.1016/0092-8674(94)90403-0. [DOI] [PubMed] [Google Scholar]
- Cullen B. R. Does HIV-1 Tat induce a change in viral initiation rights? Cell. 1993 May 7;73(3):417–420. doi: 10.1016/0092-8674(93)90126-b. [DOI] [PubMed] [Google Scholar]
- Das G., Hinkley C. S., Herr W. Basal promoter elements as a selective determinant of transcriptional activator function. Nature. 1995 Apr 13;374(6523):657–660. doi: 10.1038/374657a0. [DOI] [PubMed] [Google Scholar]
- Dynlacht B. D., Hoey T., Tjian R. Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. Cell. 1991 Aug 9;66(3):563–576. doi: 10.1016/0092-8674(81)90019-2. [DOI] [PubMed] [Google Scholar]
- 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]
- Garcia J. A., Harrich D., Soultanakis E., Wu F., Mitsuyasu R., Gaynor R. B. Human immunodeficiency virus type 1 LTR TATA and TAR region sequences required for transcriptional regulation. EMBO J. 1989 Mar;8(3):765–778. doi: 10.1002/j.1460-2075.1989.tb03437.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hauber J., Cullen B. R. Mutational analysis of the trans-activation-responsive region of the human immunodeficiency virus type I long terminal repeat. J Virol. 1988 Mar;62(3):673–679. doi: 10.1128/jvi.62.3.673-679.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heard D. J., Kiss T., Filipowicz W. Both Arabidopsis TATA binding protein (TBP) isoforms are functionally identical in RNA polymerase II and III transcription in plant cells: evidence for gene-specific changes in DNA binding specificity of TBP. EMBO J. 1993 Sep;12(9):3519–3528. doi: 10.1002/j.1460-2075.1993.tb06026.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hernandez N. Formation of the 3' end of U1 snRNA is directed by a conserved sequence located downstream of the coding region. EMBO J. 1985 Jul;4(7):1827–1837. doi: 10.1002/j.1460-2075.1985.tb03857.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hernandez N. TBP, a universal eukaryotic transcription factor? Genes Dev. 1993 Jul;7(7B):1291–1308. doi: 10.1101/gad.7.7b.1291. [DOI] [PubMed] [Google Scholar]
- Herrmann C. H., Rice A. P. Specific interaction of the human immunodeficiency virus Tat proteins with a cellular protein kinase. Virology. 1993 Dec;197(2):601–608. doi: 10.1006/viro.1993.1634. [DOI] [PubMed] [Google Scholar]
- Jakobovits A., Smith D. H., Jakobovits E. B., Capon D. J. A discrete element 3' of human immunodeficiency virus 1 (HIV-1) and HIV-2 mRNA initiation sites mediates transcriptional activation by an HIV trans activator. Mol Cell Biol. 1988 Jun;8(6):2555–2561. doi: 10.1128/mcb.8.6.2555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones K. A., Peterlin B. M. Control of RNA initiation and elongation at the HIV-1 promoter. Annu Rev Biochem. 1994;63:717–743. doi: 10.1146/annurev.bi.63.070194.003441. [DOI] [PubMed] [Google Scholar]
- 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]
- Kashanchi F., Piras G., Radonovich M. F., Duvall J. F., Fattaey A., Chiang C. M., Roeder R. G., Brady J. N. Direct interaction of human TFIID with the HIV-1 transactivator tat. Nature. 1994 Jan 20;367(6460):295–299. doi: 10.1038/367295a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Keaveney M., Berkenstam A., Feigenbutz M., Vriend G., Stunnenberg H. G. Residues in the TATA-binding protein required to mediate a transcriptional response to retinoic acid in EC cells. Nature. 1993 Oct 7;365(6446):562–566. doi: 10.1038/365562a0. [DOI] [PubMed] [Google Scholar]
- Kelleher R. J., 3rd, Flanagan P. M., Chasman D. I., Ponticelli A. S., Struhl K., Kornberg R. D. Yeast and human TFIIDs are interchangeable for the response to acidic transcriptional activators in vitro. Genes Dev. 1992 Feb;6(2):296–303. doi: 10.1101/gad.6.2.296. [DOI] [PubMed] [Google Scholar]
- Kim J. L., Nikolov D. B., Burley S. K. Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature. 1993 Oct 7;365(6446):520–527. doi: 10.1038/365520a0. [DOI] [PubMed] [Google Scholar]
- Kim Y., Geiger J. H., Hahn S., Sigler P. B. Crystal structure of a yeast TBP/TATA-box complex. Nature. 1993 Oct 7;365(6446):512–520. doi: 10.1038/365512a0. [DOI] [PubMed] [Google Scholar]
- Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Laspia M. F., Wendel P., Mathews M. B. HIV-1 Tat overcomes inefficient transcriptional elongation in vitro. J Mol Biol. 1993 Aug 5;232(3):732–746. doi: 10.1006/jmbi.1993.1427. [DOI] [PubMed] [Google Scholar]
- Lu X., Welsh T. M., Peterlin B. M. The human immunodeficiency virus type 1 long terminal repeat specifies two different transcription complexes, only one of which is regulated by Tat. J Virol. 1993 Apr;67(4):1752–1760. doi: 10.1128/jvi.67.4.1752-1760.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marciniak R. A., Calnan B. J., Frankel A. D., Sharp P. A. HIV-1 Tat protein trans-activates transcription in vitro. Cell. 1990 Nov 16;63(4):791–802. doi: 10.1016/0092-8674(90)90145-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Mermod N., O'Neill E. A., Kelly T. J., Tjian R. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989 Aug 25;58(4):741–753. doi: 10.1016/0092-8674(89)90108-6. [DOI] [PubMed] [Google Scholar]
- Muesing M. A., Smith D. H., Capon D. J. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987 Feb 27;48(4):691–701. doi: 10.1016/0092-8674(87)90247-9. [DOI] [PubMed] [Google Scholar]
- Nikolov D. B., Hu S. H., Lin J., Gasch A., Hoffmann A., Horikoshi M., Chua N. H., Roeder R. G., Burley S. K. Crystal structure of TFIID TATA-box binding protein. Nature. 1992 Nov 5;360(6399):40–46. doi: 10.1038/360040a0. [DOI] [PubMed] [Google Scholar]
- Niman H. L., Houghten R. A., Walker L. E., Reisfeld R. A., Wilson I. A., Hogle J. M., Lerner R. A. Generation of protein-reactive antibodies by short peptides is an event of high frequency: implications for the structural basis of immune recognition. Proc Natl Acad Sci U S A. 1983 Aug;80(16):4949–4953. doi: 10.1073/pnas.80.16.4949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olsen H. S., Rosen C. A. Contribution of the TATA motif to Tat-mediated transcriptional activation of human immunodeficiency virus gene expression. J Virol. 1992 Sep;66(9):5594–5597. doi: 10.1128/jvi.66.9.5594-5597.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ratnasabapathy R., Sheldon M., Johal L., Hernandez N. The HIV-1 long terminal repeat contains an unusual element that induces the synthesis of short RNAs from various mRNA and snRNA promoters. Genes Dev. 1990 Dec;4(12A):2061–2074. doi: 10.1101/gad.4.12a.2061. [DOI] [PubMed] [Google Scholar]
- Rittner K., Churcher M. J., Gait M. J., Karn J. The human immunodeficiency virus long terminal repeat includes a specialised initiator element which is required for Tat-responsive transcription. J Mol Biol. 1995 May 5;248(3):562–580. doi: 10.1006/jmbi.1995.0243. [DOI] [PubMed] [Google Scholar]
- Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
- Ruppert S., Wang E. H., Tjian R. Cloning and expression of human TAFII250: a TBP-associated factor implicated in cell-cycle regulation. Nature. 1993 Mar 11;362(6416):175–179. doi: 10.1038/362175a0. [DOI] [PubMed] [Google Scholar]
- Selby M. J., Bain E. S., Luciw P. A., Peterlin B. M. Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. Genes Dev. 1989 Apr;3(4):547–558. doi: 10.1101/gad.3.4.547. [DOI] [PubMed] [Google Scholar]
- Sheldon M., Ratnasabapathy R., Hernandez N. Characterization of the inducer of short transcripts, a human immunodeficiency virus type 1 transcriptional element that activates the synthesis of short RNAs. Mol Cell Biol. 1993 Feb;13(2):1251–1263. doi: 10.1128/mcb.13.2.1251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strubin M., Struhl K. Yeast and human TFIID with altered DNA-binding specificity for TATA elements. Cell. 1992 Feb 21;68(4):721–730. doi: 10.1016/0092-8674(92)90147-5. [DOI] [PubMed] [Google Scholar]
- Subramanian T., D'Sa-Eipper C., Elangovan B., Chinnadurai G. The activation region of the Tat protein of human immunodeficiency virus type-1 functions in yeast. Nucleic Acids Res. 1994 Apr 25;22(8):1496–1499. doi: 10.1093/nar/22.8.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tanaka M., Herr W. Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation. Cell. 1990 Feb 9;60(3):375–386. doi: 10.1016/0092-8674(90)90589-7. [DOI] [PubMed] [Google Scholar]
- Tanese N., Pugh B. F., Tjian R. Coactivators for a proline-rich activator purified from the multisubunit human TFIID complex. Genes Dev. 1991 Dec;5(12A):2212–2224. doi: 10.1101/gad.5.12a.2212. [DOI] [PubMed] [Google Scholar]
- Tansey W. P., Herr W. The ability to associate with activation domains in vitro is not required for the TATA box-binding protein to support activated transcription in vivo. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10550–10554. doi: 10.1073/pnas.92.23.10550. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tansey W. P., Ruppert S., Tjian R., Herr W. Multiple regions of TBP participate in the response to transcriptional activators in vivo. Genes Dev. 1994 Nov 15;8(22):2756–2769. doi: 10.1101/gad.8.22.2756. [DOI] [PubMed] [Google Scholar]
- Tjian R., Maniatis T. Transcriptional activation: a complex puzzle with few easy pieces. Cell. 1994 Apr 8;77(1):5–8. doi: 10.1016/0092-8674(94)90227-5. [DOI] [PubMed] [Google Scholar]
- Triezenberg S. J., Kingsbury R. C., McKnight S. L. Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression. Genes Dev. 1988 Jun;2(6):718–729. doi: 10.1101/gad.2.6.718. [DOI] [PubMed] [Google Scholar]
- Webster N., Jin J. R., Green S., Hollis M., Chambon P. The yeast UASG is a transcriptional enhancer in human HeLa cells in the presence of the GAL4 trans-activator. Cell. 1988 Jan 29;52(2):169–178. doi: 10.1016/0092-8674(88)90505-3. [DOI] [PubMed] [Google Scholar]
- Weinzierl R. O., Dynlacht B. D., Tjian R. Largest subunit of Drosophila transcription factor IID directs assembly of a complex containing TBP and a coactivator. Nature. 1993 Apr 8;362(6420):511–517. doi: 10.1038/362511a0. [DOI] [PubMed] [Google Scholar]
- White J. H., Brou C., Wu J., Burton N., Egly J. M., Chambon P. Evidence for a factor required for transcriptional stimulation by the chimeric acidic activator GAL-VP16 in HeLa cell extracts. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7674–7678. doi: 10.1073/pnas.88.17.7674. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhou Q., Boyer T. G., Berk A. J. Factors (TAFs) required for activated transcription interact with TATA box-binding protein conserved core domain. Genes Dev. 1993 Feb;7(2):180–187. doi: 10.1101/gad.7.2.180. [DOI] [PubMed] [Google Scholar]
- Zhou Q., Sharp P. A. Novel mechanism and factor for regulation by HIV-1 Tat. EMBO J. 1995 Jan 16;14(2):321–328. doi: 10.1002/j.1460-2075.1995.tb07006.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zoller M. J., Smith M. Oligonucleotide-directed mutagenesis using M13-derived vectors: an efficient and general procedure for the production of point mutations in any fragment of DNA. Nucleic Acids Res. 1982 Oct 25;10(20):6487–6500. doi: 10.1093/nar/10.20.6487. [DOI] [PMC free article] [PubMed] [Google Scholar]