This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by D'Agostino, D M
Right arrow Articles by Pavlakis, G N
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by D'Agostino, D M
Right arrow Articles by Pavlakis, G N

 Previous Article  |  Next Article 

Mol Cell Biol. 1992 March; 12(3): 1375-1386

The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag/pol and vpu/env mRNAs.

D M D'Agostino, B K Felber, J E Harrison and G N Pavlakis

Human Retrovirus Section, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702.

ABSTRACT

Biochemical examination of the Rev-dependent expression of gag mRNAs produced from gag-Rev-responsive element (RRE) expression plasmids showed a large discrepancy between the level of cytoplasmic gag mRNA and the produced Gag protein. Significant levels of the mRNA produced in the absence of Rev were localized in the cytoplasm, while very low levels of Gag protein were produced. In the presence of Rev, the levels of mRNA increased by 4- to 16-fold, while the Gag protein production increased by 800-fold. These findings indicated that in addition to promoting nucleus-to-cytoplasm transport, Rev increased the utilization of cytoplasmic viral mRNA. Poly(A) selection and in vitro translation of cytoplasmic gag mRNA verified that the mRNA produced in the absence of Rev was functional. To analyze the translational defect in the absence of Rev, we examined the association of the cytoplasmic gag mRNA with ribosomes. gag mRNA produced in the absence of Rev was excluded from polysomes, while gag mRNA produced in the presence of Rev was associated with polysomes and produced Gag protein. These observations showed that the presence of Rev was required for efficient loading of gag mRNA onto polysomes. This effect required the presence of the RRE on the mRNA. Analysis of mRNAs produced from a rev-minus proviral clone confirmed that the presence of Rev promoted polysomal loading of both gag/pol and vpu/env mRNAs. The localization of gag mRNA was also examined by in situ hybridization. This analysis showed that in the presence of Rev, most of the gag mRNA was found in the cytoplasm, while in the absence of Rev, most of the gag mRNA was found in the nucleus and in the region surrounding the nucleus. These results suggest that a substantial fraction of the gag mRNA is retained in distinct cytoplasmic compartments in the absence and presence of Rev. These findings indicate that the presence of Rev is required along the entire mRNA transport and utilization pathway for the stabilization, correct localization, and efficient translation of RRE-containing mRNAs.

Mol Cell Biol. 1992 March; 12(3): 1375-1386




This article has been cited by other articles:

  • Nitta, T., Hofacre, A., Hull, S., Fan, H. (2009). Identification and Mutational Analysis of a Rej Response Element in Jaagsiekte Sheep Retrovirus RNA. J. Virol. 83: 12499-12511 [Abstract] [Full Text]  
  • Hofacre, A., Nitta, T., Fan, H. (2009). Jaagsiekte Sheep Retrovirus Encodes a Regulatory Factor, Rej, Required for Synthesis of Gag Protein. J. Virol. 83: 12483-12498 [Abstract] [Full Text]  
  • Hadian, K., Vincendeau, M., Mausbacher, N., Nagel, D., Hauck, S. M., Ueffing, M., Loyter, A., Werner, T., Wolff, H., Brack-Werner, R. (2009). Identification of a Heterogeneous Nuclear Ribonucleoprotein-recognition Region in the HIV Rev Protein. J. Biol. Chem. 284: 33384-33391 [Abstract] [Full Text]  
  • Vallejos, M., Ramdohr, P., Valiente-Echeverria, F., Tapia, K., Rodriguez, F. E., Lowy, F., Huidobro-Toro, J. P., Dangerfield, J. A., Lopez-Lastra, M. (2009). The 5'-untranslated region of the mouse mammary tumor virus mRNA exhibits cap-independent translation initiation. Nucleic Acids Res 0: gkp890v1-gkp890 [Abstract] [Full Text]  
  • Iyer, S. R., Yu, D., Biancotto, A., Margolis, L. B., Wu, Y. (2009). Measurement of Human Immunodeficiency Virus Type 1 Preintegration Transcription by Using Rev-Dependent Rev-CEM Cells Reveals a Sizable Transcribing DNA Population Comparable to That from Proviral Templates. J. Virol. 83: 8662-8673 [Abstract] [Full Text]  
  • Groom, H. C. T., Anderson, E. C., Lever, A. M. L. (2009). Rev: beyond nuclear export. J. Gen. Virol. 90: 1303-1318 [Abstract] [Full Text]  
  • Caporale, M., Arnaud, F., Mura, M., Golder, M., Murgia, C., Palmarini, M. (2009). The Signal Peptide of a Simple Retrovirus Envelope Functions as a Posttranscriptional Regulator of Viral Gene Expression. J. Virol. 83: 4591-4604 [Abstract] [Full Text]  
  • Groom, H. C. T., Anderson, E. C., Dangerfield, J. A., Lever, A. M. L. (2009). Rev regulates translation of human immunodeficiency virus type 1 RNAs. J. Gen. Virol. 90: 1141-1147 [Abstract] [Full Text]  
  • Legiewicz, M., Badorrek, C. S., Turner, K. B., Fabris, D., Hamm, T. E., Rekosh, D., Hammarskjold, M.-L., Le Grice, S. F. J. (2008). Resistance to RevM10 inhibition reflects a conformational switch in the HIV-1 Rev response element. Proc. Natl. Acad. Sci. USA 105: 14365-14370 [Abstract] [Full Text]  
  • Shuck-Lee, D., Chen, F. F., Willard, R., Raman, S., Ptak, R., Hammarskjold, M.-L., Rekosh, D. (2008). Heterocyclic Compounds That Inhibit Rev-RRE Function and Human Immunodeficiency Virus Type 1 Replication. Antimicrob. Agents Chemother. 52: 3169-3179 [Abstract] [Full Text]  
  • Ajamian, L., Abrahamyan, L., Milev, M., Ivanov, P. V., Kulozik, A. E., Gehring, N. H., Mouland, A. J. (2008). Unexpected roles for UPF1 in HIV-1 RNA metabolism and translation. RNA 14: 914-927 [Abstract] [Full Text]  
  • Greatorex, J. S., Palmer, E. A., Pomerantz, R. J., Dangerfield, J. A., Lever, A. M. L. (2006). Mutation of the Rev-binding loop in the human immunodeficiency virus 1 leader causes a replication defect characterized by altered RNA trafficking and packaging.. J. Gen. Virol. 87: 3039-3044 [Abstract] [Full Text]  
  • Bohne, J., Wodrich, H., Kräusslich, H.-G. (2005). Splicing of human immunodeficiency virus RNA is position-dependent suggesting sequential removal of introns from the 5' end. Nucleic Acids Res 33: 825-837 [Abstract] [Full Text]  
  • Whitfield, M. L., Kaygun, H., Erkmann, J. A., Townley-Tilson, W. H. D., Dominski, Z., Marzluff, W. F. (2004). SLBP is associated with histone mRNA on polyribosomes as a component of the histone mRNP. Nucleic Acids Res 32: 4833-4842 [Abstract] [Full Text]  
  • Sanchez-Velar, N., Udofia, E. B., Yu, Z., Zapp, M. L. (2004). hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region. Genes Dev. 18: 23-34 [Abstract] [Full Text]  
  • Gallego, J., Greatorex, J., Zhang, H., Yang, B., Arunachalam, S., Fang, J., Seamons, J., Lea, S., Pomerantz, R. J., Lever, A. M. L. (2003). Rev Binds Specifically to a Purine Loop in the SL1 Region of the HIV-1 Leader RNA. J. Biol. Chem. 278: 40385-40391 [Abstract] [Full Text]  
  • Zolotukhin, A. S., Michalowski, D., Bear, J., Smulevitch, S. V., Traish, A. M., Peng, R., Patton, J., Shatsky, I. N., Felber, B. K. (2003). PSF Acts through the Human Immunodeficiency Virus Type 1 mRNA Instability Elements To Regulate Virus Expression. Mol. Cell. Biol. 23: 6618-6630 [Abstract] [Full Text]  
  • Wiklund, L., Sokolowski, M., Carlsson, A., Rush, M., Schwartz, S. (2002). Inhibition of Translation by UAUUUAU and UAUUUUUAU Motifs of the AU-rich RNA Instability Element in the HPV-1 Late 3' Untranslated Region. J. Biol. Chem. 277: 40462-40471 [Abstract] [Full Text]  
  • Dangel, A. W., Hull, S., Roberts, T. M., Boris-Lawrie, K. (2002). Nuclear Interactions Are Necessary for Translational Enhancement by Spleen Necrosis Virus RU5. J. Virol. 76: 3292-3300 [Abstract] [Full Text]  
  • Yi, R., Bogerd, H. P., Cullen, B. R. (2002). Recruitment of the Crm1 Nuclear Export Factor Is Sufficient To Induce Cytoplasmic Expression of Incompletely Spliced Human Immunodeficiency Virus mRNAs. J. Virol. 76: 2036-2042 [Abstract] [Full Text]  
  • Zolotukhin, A. S., Tan, W., Bear, J., Smulevitch, S., Felber, B. K. (2002). U2AF Participates in the Binding of TAP (NXF1) to mRNA. J. Biol. Chem. 277: 3935-3942 [Abstract] [Full Text]  
  • Barber, S. A., Bruett, L., Douglass, B. R., Herbst, D. S., Zink, M. C., Clements, J. E. (2002). Visna Virus-Induced Activation of MAPK Is Required for Virus Replication and Correlates with Virus-Induced Neuropathology. J. Virol. 76: 817-828 [Abstract] [Full Text]  
  • Magin-Lachmann, C., Hahn, S., Strobel, H., Held, U., Lower, J., Lower, R. (2001). Rec (Formerly Corf) Function Requires Interaction with a Complex, Folded RNA Structure within Its Responsive Element rather than Binding to a Discrete Specific Binding Site. J. Virol. 75: 10359-10371 [Abstract] [Full Text]  
  • Aquaro, S., Panti, S., Caroleo, M. C., Balestra, E., Cenci, A., Forbici, F., Ippolito, G., Mastino, A., Testi, R., Mollace, V., Calio, R., Perno, C. F. (2000). Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes. J. Leukoc. Biol. 68: 429-435 [Abstract] [Full Text]  
  • Roberts, T. M., Boris-Lawrie, K. (2000). The 5' RNA Terminus of Spleen Necrosis Virus Stimulates Translation of Nonviral mRNA. J. Virol. 74: 8111-8118 [Abstract] [Full Text]  
  • Michienzi, A., Cagnon, L., Bahner, I., Rossi, J. J. (2000). Ribozyme-mediated inhibition of HIV 1 suggests nucleolar trafficking of HIV-1 RNA. Proc. Natl. Acad. Sci. USA 97: 8955-8960 [Abstract] [Full Text]  
  • Kotsopoulou, E., Kim, V. N., Kingsman, A. J., Kingsman, S. M., Mitrophanous, K. A. (2000). A Rev-Independent Human Immunodeficiency Virus Type 1 (HIV-1)-Based Vector That Exploits a Codon-Optimized HIV-1 gag-pol Gene. J. Virol. 74: 4839-4852 [Abstract] [Full Text]  
  • Magin, C., Lower, R., Lower, J. (1999). cORF and RcRE, the Rev/Rex and RRE/RxRE Homologues of the Human Endogenous Retrovirus Family HTDV/HERV-K. J. Virol. 73: 9496-9507 [Abstract] [Full Text]  
  • Kusuhara, K., Anderson, M., Pettiford, S. M., Green, P. L. (1999). Human T-Cell Leukemia Virus Type 2 Rex Protein Increases Stability and Promotes Nuclear to Cytoplasmic Transport of gag/pol and env RNAs. J. Virol. 73: 8112-8119 [Abstract] [Full Text]  
  • Szilvay, A. M., Bøe, S.-O., Kalland, K.-H. (1999). Co-expression of a trans-dominant negative mutant of the human immunodeficiency virus type 1 (HIV-1) Rev protein affects the Rev-dependent splicing pattern and expression of HIV-1 RNAs. J. Gen. Virol. 80: 1965-1974 [Abstract] [Full Text]  
  • Harada, J. N., Berk, A. J. (1999). p53-Independent and -Dependent Requirements for E1B-55K in Adenovirus Type 5 Replication. J. Virol. 73: 5333-5344 [Abstract] [Full Text]  
  • Butsch, M., Hull, S., Wang, Y., Roberts, T. M., Boris-Lawrie, K. (1999). The 5' RNA Terminus of Spleen Necrosis Virus Contains a Novel Posttranscriptional Control Element That Facilitates Human Immunodeficiency Virus Rev/RRE-Independent Gag Production. J. Virol. 73: 4847-4855 [Abstract] [Full Text]  
  • Choudhury, I, Wang, J, Stein, S, Rabson, A, Leibowitz, M. (1999). Translational effects of peptide antagonists of Tat protein of human immunodeficiency virus type 1. J. Gen. Virol. 80: 777-782 [Abstract]  
  • Ogert, R. A., Beemon, K. L. (1998). Mutational Analysis of the Rous Sarcoma Virus DR Posttranscriptional Control Element. J. Virol. 72: 3407-3411 [Abstract] [Full Text]  
  • Afonina, E., Neumann, M., Pavlakis, G. N. (1997). Preferential Binding of Poly(A)-binding Protein 1to an Inhibitory RNA Element in the Human Immunodeficiency Virus Type 1gag mRNA. J. Biol. Chem. 272: 2307-2311 [Abstract] [Full Text]  
  • Dyhr-Mikkelsen, H., Kjems, Jør. (1995). Inefficient Spliceosome Assembly and Abnormal Branch Site Selection in Splicing of an HIV-1 Transcript in Vitro. J. Biol. Chem. 270: 24060-24066 [Abstract] [Full Text]  
  • Jensen, T. H., Leffers, H., Kjems, J (1995). Intermolecular Binding Sites of Human Immunodeficiency Virus Type 1 Rev Protein Determined by Protein Footprinting. J. Biol. Chem. 270: 13777-13784 [Abstract] [Full Text]  
  • Dundr, M, Leno, G., Hammarskjold, M., Rekosh, D, Helga-Maria, C, Olson, M. (1995). The roles of nucleolar structure and function in the subcellular location of the HIV-1 Rev protein. J. Cell Sci. 108: 2811-2823 [Abstract]  
  • Constantoulakis, P, Campbell, M, Felber, B., Nasioulas, G, Afonina, E, Pavlakis, G. (1993). Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene. Science 259: 1314-1318 [Abstract]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»