This Article
Right arrow Full Text
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 Cupelli, L.
Right arrow Articles by Lenz, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cupelli, L.
Right arrow Articles by Lenz, J.

 Previous Article  |  Next Article 

Journal of Virology, October 1998, p. 7807-7814, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Secondary Structure of the R Region of a Murine Leukemia Virus Is Important for Stimulation of Long Terminal Repeat-Driven Gene Expression

Lisa Cupelli,dagger Sharon A. Okenquist,Dagger Alla Trubetskoy, and Jack Lenz*

Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461

Received 12 May 1998/Accepted 24 June 1998

In addition to their role in reverse transcription, the R-region sequences of some retroviruses affect viral transcription. The first 28 nucleotides of the R region within the long terminal repeat (LTR) of the murine type C retrovirus SL3 were predicted to form a stem-loop structure. We tested whether this structure affected the transcriptional activity of the viral LTR. Mutations that altered either side of the stem and thus disrupted base pairing were generated. These decreased the level of expression of a reporter gene under the control of viral LTR sequences about 5-fold in transient expression assays and 10-fold in cells stably transformed with the LTR-reporter plasmids. We also generated a compensatory mutant in which both the ascending and descending sides of the stem were mutated such that the nucleotide sequence was different but the predicted secondary structure was maintained. Most of the activity of the wild-type SL3 element was restored in this mutant. Thus, the stem-loop structure was important for the maximum activity of the SL3 LTR. Primer extension analysis indicated that the stem-loop structure affected the levels of cytoplasmic RNA. Nuclear run-on assays indicated that deletion of the R region had a small effect on transcriptional initiation and no effect on RNA polymerase processivity. Thus, the main effect of the R-region element was on one or more steps that occurred after the template was transcribed by RNA polymerase. This finding implied that the main function of the R-region element involved RNA processing. R-region sequences of human immunodeficiency virus type 1 or mouse mammary tumor virus could not replace the SL3 element. R-region sequences from an avian reticuloendotheliosis virus partially substituted for the SL3 sequences. R-region sequences from Moloney murine leukemia virus or feline leukemia virus did function in place of the SL3 element. Thus, the R region element appears to be a general feature of the mammalian type C genus of retroviruses.

* Corresponding author. Mailing address: Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-3715. Fax: (718) 430-8778. E-mail: lenz{at}aecom.yu.edu.

dagger Present address: Hoffmann-La Roche Inc., Nutley, NJ 07110.

Dagger Present address: Regeneron Pharmaceuticals, Tarrytown, NY 10591.

Journal of Virology, October 1998, p. 7807-7814, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Metzl, C., Mischek, D., Salmons, B., Gunzburg, W. H., Renner, M., Portsmouth, D. (2006). Tissue- and Tumor-Specific Targeting of Murine Leukemia Virus-Based Replication-Competent Retroviral Vectors. J. Virol. 80: 7070-7078 [Abstract] [Full Text]  
  • Swindle, C. S., Kim, H. G., Klug, C. A. (2004). Mutation of CpGs in the Murine Stem Cell Virus Retroviral Vector Long Terminal Repeat Represses Silencing in Embryonic Stem Cells. J. Biol. Chem. 279: 34-41 [Abstract] [Full Text]  
  • Chao, S.-H., Walker, J. R., Chanda, S. K., Gray, N. S., Caldwell, J. S. (2003). Identification of Homeodomain Proteins, PBX1 and PREP1, Involved in the Transcription of Murine Leukemia Virus. Mol. Cell. Biol. 23: 831-841 [Abstract] [Full Text]  
  • Scheef, G., Fischer, N., Flory, E., Schmitt, I., Tonjes, R. R. (2002). Transcriptional Regulation of Porcine Endogenous Retroviruses Released from Porcine and Infected Human Cells by Heterotrimeric Protein Complex NF-Y and Impact of Immunosuppressive Drugs. J. Virol. 76: 12553-12563 [Abstract] [Full Text]  
  • Furger, A., Monks, J., Proudfoot, N. J. (2001). The Retroviruses Human Immunodeficiency Virus Type 1 and Moloney Murine Leukemia Virus Adopt Radically Different Strategies To Regulate Promoter-Proximal Polyadenylation. J. Virol. 75: 11735-11746 [Abstract] [Full Text]  
  • Ghosh, S. K., Roy-Burman, P., Faller, D. V. (2000). Long Terminal Repeat Regions from Exogenous but Not Endogenous Feline Leukemia Viruses Transactivate Cellular Gene Expression. J. Virol. 74: 9742-9748 [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]  
  • Palmarini, M., Datta, S., Omid, R., Murgia, C., Fan, H. (2000). The Long Terminal Repeat of Jaagsiekte Sheep Retrovirus Is Preferentially Active in Differentiated Epithelial Cells of the Lungs. J. Virol. 74: 5776-5787 [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]  
  • Trubetskoy, A. M., Okenquist, S. A., Lenz, J. (1999). R Region Sequences in the Long Terminal Repeat of a Murine Retrovirus Specifically Increase Expression of Unspliced RNAs. J. Virol. 73: 3477-3483 [Abstract] [Full Text]  


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