Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: mapping cryptic functions of the arginine-rich motif
- PMID: 2217212
- PMCID: PMC54833
- DOI: 10.1073/pnas.87.19.7787
Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: mapping cryptic functions of the arginine-rich motif
Abstract
The human immunodeficiency virus type 1 (HIV-1) transactivator Rev is a nuclear protein that regulates expression of certain HIV-1 transcripts by binding to an RNA target element (the RRE) present in these transcripts. A short arginine-rich sequence in Rev contains the signals required to direct this protein into nuclei, where it associates preferentially with nucleoli. We created a steroid-inducible transactivator by fusing Rev with the steroid-binding domain of the glucocorticoid receptor (GR). This Rev/GR protein remains inactive in the cytoplasm when steroids are absent, but it enters the nucleus and initiates transactivation within minutes after exposure to dexamethasone. Although the GR moiety is sufficient to transport Rev/GR into nuclei, mutation of certain residues in the arginine-rich region blocks nucleolar localization and also inhibits transactivation. We find that other mutations in this region, however, can abolish the function of Rev/GR without affecting its localization; the latter phenotype may reflect a specific defect in binding of the RRE.
Similar articles
-
Exchange of the basic domain of human immunodeficiency virus type 1 Rev for a polyarginine stretch expands the RNA binding specificity, and a minimal arginine cluster is required for optimal RRE RNA binding affinity, nuclear accumulation, and trans-activation.J Virol. 2001 Mar;75(6):2957-71. doi: 10.1128/JVI.75.6.2957-2971.2001. J Virol. 2001. PMID: 11222721 Free PMC article.
-
Oligomerization and RNA binding domains of the type 1 human immunodeficiency virus Rev protein: a dual function for an arginine-rich binding motif.Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7734-8. doi: 10.1073/pnas.88.17.7734. Proc Natl Acad Sci U S A. 1991. PMID: 1715576 Free PMC article.
-
HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency.Cell. 1991 Apr 19;65(2):241-8. doi: 10.1016/0092-8674(91)90158-u. Cell. 1991. PMID: 2015625
-
PRMT6 diminishes HIV-1 Rev binding to and export of viral RNA.Retrovirology. 2006 Dec 18;3:93. doi: 10.1186/1742-4690-3-93. Retrovirology. 2006. PMID: 17176473 Free PMC article.
-
Inhibition of HIV-1 replication by targeting the Rev protein.Leukemia. 1997 Apr;11 Suppl 3:134-7. Leukemia. 1997. PMID: 9209321 Review.
Cited by
-
Transfer of the UAP56 interaction motif of human cytomegalovirus pUL69 to its murine cytomegalovirus homolog converts the protein into a functional mRNA export factor that can substitute for pUL69 during viral infection.J Virol. 2012 Jul;86(13):7448-53. doi: 10.1128/JVI.00730-12. Epub 2012 May 2. J Virol. 2012. PMID: 22553320 Free PMC article.
-
Expression of exogenous Sam68, the 68-kilodalton SRC-associated protein in mitosis, is able to alleviate impaired Rev function in astrocytes.J Virol. 2002 May;76(9):4526-35. doi: 10.1128/jvi.76.9.4526-4535.2002. J Virol. 2002. PMID: 11932418 Free PMC article.
-
Characterization of human immunodeficiency virus-1 (HIV-1) rev by (time-resolved) fluorescence spectroscopy.J Fluoresc. 1994 Dec;4(4):299-302. doi: 10.1007/BF01881444. J Fluoresc. 1994. PMID: 24233603
-
HIV Rev-dependent binding of SF2/ASF to the Rev response element: possible role in Rev-mediated inhibition of HIV RNA splicing.Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):973-8. doi: 10.1073/pnas.94.3.973. Proc Natl Acad Sci U S A. 1997. PMID: 9023367 Free PMC article.
-
Role of polyadenylation in nucleocytoplasmic transport of mRNA.Mol Cell Biol. 1996 Apr;16(4):1534-42. doi: 10.1128/MCB.16.4.1534. Mol Cell Biol. 1996. PMID: 8657127 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources