Abstract
The RNAs of the hepatitis B virus (HBV) contain a cis-acting regulatory element which facilitates the cytoplasmic localization of unspliced transcripts (J. Huang and T. J. Liang, Mol. Cell. Biol. 13:7476-7486, 1993, and Z. M. Huang and T. S. Yen, J. Virl. 68:3193-3199, 1994). Such localization is presumed to be mediated by cellular factors which interact with the element. The HBV posttranscriptional regulatory element (HBVPRE) can efficiently activate an RNA export reporter system in an orientation-dependent and position-independent manner. Deletion analysis reveals that the HBVPRE consists of two subelements which function synergistically. A synergistic effect was also observed when the 5' (PREalpha) or 3' (PREbeta) subelements were duplicated. The bipartite structure of the HBVPRE is reminiscent of reports that the high-affinity binding sites of the Rev-like proteins must be duplicated to function efficiently (M. Grone, E. Hoffmann, S. Berchtold, B.R. Cullen, and R. Grassmann, Virology 204:144-152, 1994; X. Huang, T.J. Hope, B.L. Bond, D. McDonald, K. Grahl, and T. G. Parslow, J. Virol. 65:2131-2134, 1991; and D. McDonald, T. J. Hope, and T. G. Parslow, J. Virol. 66:7232-7238, 1992).
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- Ahmed Y. F., Hanly S. M., Malim M. H., Cullen B. R., Greene W. C. Structure-function analyses of the HTLV-I Rex and HIV-1 Rev RNA response elements: insights into the mechanism of Rex and Rev action. Genes Dev. 1990 Jun;4(6):1014–1022. doi: 10.1101/gad.4.6.1014. [DOI] [PubMed] [Google Scholar]
- Bartel D. P., Zapp M. L., Green M. R., Szostak J. W. HIV-1 Rev regulation involves recognition of non-Watson-Crick base pairs in viral RNA. Cell. 1991 Nov 1;67(3):529–536. doi: 10.1016/0092-8674(91)90527-6. [DOI] [PubMed] [Google Scholar]
- Bray M., Prasad S., Dubay J. W., Hunter E., Jeang K. T., Rekosh D., Hammarskjöld M. L. A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256–1260. doi: 10.1073/pnas.91.4.1256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen P. J., Chen C. R., Sung J. L., Chen D. S. Identification of a doubly spliced viral transcript joining the separated domains for putative protease and reverse transcriptase of hepatitis B virus. J Virol. 1989 Oct;63(10):4165–4171. doi: 10.1128/jvi.63.10.4165-4171.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cullen B. R. Human immunodeficiency virus as a prototypic complex retrovirus. J Virol. 1991 Mar;65(3):1053–1056. doi: 10.1128/jvi.65.3.1053-1056.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Fischer U., Meyer S., Teufel M., Heckel C., Lührmann R., Rautmann G. Evidence that HIV-1 Rev directly promotes the nuclear export of unspliced RNA. EMBO J. 1994 Sep 1;13(17):4105–4112. doi: 10.1002/j.1460-2075.1994.tb06728.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ganem D., Varmus H. E. The molecular biology of the hepatitis B viruses. Annu Rev Biochem. 1987;56:651–693. doi: 10.1146/annurev.bi.56.070187.003251. [DOI] [PubMed] [Google Scholar]
- Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gröne M., Hoffmann E., Berchtold S., Cullen B. R., Grassmann R. A single stem-loop structure within the HTLV-1 Rex response element is sufficient to mediate Rex activity in vivo. Virology. 1994 Oct;204(1):144–152. doi: 10.1006/viro.1994.1518. [DOI] [PubMed] [Google Scholar]
- Hantz O., Baginski I., Fourel I., Chemin I., Trepo C. Viral spliced RNA are produced, encapsidated and reverse transcribed during in vivo woodchuck hepatitis virus infection. Virology. 1992 Sep;190(1):193–200. doi: 10.1016/0042-6822(92)91205-9. [DOI] [PubMed] [Google Scholar]
- Heaphy S., Finch J. T., Gait M. J., Karn J., Singh M. Human immunodeficiency virus type 1 regulator of virion expression, rev, forms nucleoprotein filaments after binding to a purine-rich "bubble" located within the rev-responsive region of viral mRNAs. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7366–7370. doi: 10.1073/pnas.88.16.7366. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Hope T. J., Huang X. J., McDonald D., Parslow T. G. Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: mapping cryptic functions of the arginine-rich motif. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7787–7791. doi: 10.1073/pnas.87.19.7787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang J., Liang T. J. A novel hepatitis B virus (HBV) genetic element with Rev response element-like properties that is essential for expression of HBV gene products. Mol Cell Biol. 1993 Dec;13(12):7476–7486. doi: 10.1128/mcb.13.12.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Huang Z. M., Yen T. S. Hepatitis B virus RNA element that facilitates accumulation of surface gene transcripts in the cytoplasm. J Virol. 1994 May;68(5):3193–3199. doi: 10.1128/jvi.68.5.3193-3199.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang Z. M., Yen T. S. Role of the hepatitis B virus posttranscriptional regulatory element in export of intronless transcripts. Mol Cell Biol. 1995 Jul;15(7):3864–3869. doi: 10.1128/mcb.15.7.3864. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korb M., Ke Y., Johnson L. F. Stimulation of gene expression by introns: conversion of an inhibitory intron to a stimulatory intron by alteration of the splice donor sequence. Nucleic Acids Res. 1993 Dec 25;21(25):5901–5908. doi: 10.1093/nar/21.25.5901. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu X., Mertz J. E. HnRNP L binds a cis-acting RNA sequence element that enables intron-dependent gene expression. Genes Dev. 1995 Jul 15;9(14):1766–1780. doi: 10.1101/gad.9.14.1766. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- McDonald D., Hope T. J., Parslow T. G. Posttranscriptional regulation by the human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex proteins through a heterologous RNA binding site. J Virol. 1992 Dec;66(12):7232–7238. doi: 10.1128/jvi.66.12.7232-7238.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nassal M., Schaller H. Hepatitis B virus replication. Trends Microbiol. 1993 Sep;1(6):221–228. doi: 10.1016/0966-842x(93)90136-f. [DOI] [PubMed] [Google Scholar]
- Okayama H., Berg P. A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells. Mol Cell Biol. 1983 Feb;3(2):280–289. doi: 10.1128/mcb.3.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Purcell D. F., Martin M. A. Alternative splicing of human immunodeficiency virus type 1 mRNA modulates viral protein expression, replication, and infectivity. J Virol. 1993 Nov;67(11):6365–6378. doi: 10.1128/jvi.67.11.6365-6378.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarvetnick N., Liggitt D., Pitts S. L., Hansen S. E., Stewart T. A. Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma. Cell. 1988 Mar 11;52(5):773–782. doi: 10.1016/0092-8674(88)90414-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Su T. S., Lai C. J., Huang J. L., Lin L. H., Yauk Y. K., Chang C. M., Lo S. J., Han S. H. Hepatitis B virus transcript produced by RNA splicing. J Virol. 1989 Sep;63(9):4011–4018. doi: 10.1128/jvi.63.9.4011-4018.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tan W., Schwartz S. The Rev protein of human immunodeficiency virus type 1 counteracts the effect of an AU-rich negative element in the human papillomavirus type 1 late 3' untranslated region. J Virol. 1995 May;69(5):2932–2945. doi: 10.1128/jvi.69.5.2932-2945.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tiley L. S., Malim M. H., Cullen B. R. Conserved functional organization of the human immunodeficiency virus type 1 and visna virus Rev proteins. J Virol. 1991 Jul;65(7):3877–3881. doi: 10.1128/jvi.65.7.3877-3881.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Zapp M. L., Stern S., Green M. R. Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production. Cell. 1993 Sep 24;74(6):969–978. doi: 10.1016/0092-8674(93)90720-b. [DOI] [PubMed] [Google Scholar]
- Zolotukhin A. S., Valentin A., Pavlakis G. N., Felber B. K. Continuous propagation of RRE(-) and Rev(-)RRE(-) human immunodeficiency virus type 1 molecular clones containing a cis-acting element of simian retrovirus type 1 in human peripheral blood lymphocytes. J Virol. 1994 Dec;68(12):7944–7952. doi: 10.1128/jvi.68.12.7944-7952.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]