This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tan, W. Articles by Schwartz, S. Search for Related Content PubMed PubMed Citation Articles by Tan, W. Articles by Schwartz, S.

 Previous Article  |  Next Article 

J. Virol., 05 1995, 2932-2945, Vol 69, No. 5
Copyright © 1995, American Society for Microbiology

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

W Tan and S Schwartz
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.

We have identified a sequence in the late 3' untranslated region of human papillomavirus type 1 mRNAs that acts posttranscriptionally to repress gene expression. Deletion analysis localized the inhibitory element to an AU-rich sequence between nucleotides 6958 and 6984 on the human papillomavirus type 1 genome. This sequence inhibits gene expression in an orientation-dependent manner. Upon transfection of eucaryotic cells with plasmids containing this sequence, approximately 4-fold-lower cytoplasmic mRNA levels and 64- to 128-fold-lower protein levels were produced compared with those produced by plasmids lacking the inhibitory sequence. Interestingly, providing the constitutive transport element of simian retrovirus type 1 in sense orientation counteracted inhibition exerted by the human papillomavirus type 1 sequence. Inhibition could also be overcome by the presence of human immunodeficiency virus type 1 Rev protein in trans and its target sequence, the Rev-responsive element, in cis. Rev is a nuclear protein and acts by promoting nuclear export of human immunodeficiency virus type 1 mRNAs encoding structural proteins. Our results are consistent with a model for human papillomavirus type 1 late-gene expression in which mRNAs containing human papillomavirus type 1 inhibitory sequences enter a nonproductive route in the nucleus, resulting in inefficient mRNA utilization. Rev directs mRNA containing inhibitory sequences to a productive route by interacting with the Rev-responsive element.

This article has been cited by other articles:

• Somberg, M., Zhao, X., Frohlich, M., Evander, M., Schwartz, S. (2008). Polypyrimidine Tract Binding Protein Induces Human Papillomavirus Type 16 Late Gene Expression by Interfering with Splicing Inhibitory Elements at the Major Late 5' Splice Site, SD3632. J. Virol. 82: 3665-3678 [Abstract] [Full Text]  
• Rush, M., Zhao, X., Schwartz, S. (2005). A Splicing Enhancer in the E4 Coding Region of Human Papillomavirus Type 16 Is Required for Early mRNA Splicing and Polyadenylation as Well as Inhibition of Premature Late Gene Expression. J. Virol. 79: 12002-12015 [Abstract] [Full Text]  
• Oberg, D., Fay, J., Lambkin, H., Schwartz, S. (2005). A Downstream Polyadenylation Element in Human Papillomavirus Type 16 L2 Encodes Multiple GGG Motifs and Interacts with hnRNP H. J. Virol. 79: 9254-9269 [Abstract] [Full Text]  
• Zhao, X., Oberg, D., Rush, M., Fay, J., Lambkin, H., Schwartz, S. (2005). A 57-Nucleotide Upstream Early Polyadenylation Element in Human Papillomavirus Type 16 Interacts with hFip1, CstF-64, hnRNP C1/C2, and Polypyrimidine Tract Binding Protein. J. Virol. 79: 4270-4288 [Abstract] [Full Text]  
• Zhao, X., Rush, M., Schwartz, S. (2004). Identification of an hnRNP A1-Dependent Splicing Silencer in the Human Papillomavirus Type 16 L1 Coding Region That Prevents Premature Expression of the Late L1 Gene. J. Virol. 78: 10888-10905 [Abstract] [Full Text]  
• Buck, C. B., Pastrana, D. V., Lowy, D. R., Schiller, J. T. (2004). Efficient Intracellular Assembly of Papillomaviral Vectors. J. Virol. 78: 751-757 [Abstract] [Full Text]  
• Oberg, D., Collier, B., Zhao, X., Schwartz, S. (2003). Mutational Inactivation of Two Distinct Negative RNA Elements in the Human Papillomavirus Type 16 L2 Coding Region Induces Production of High Levels of L2 in Human Cells. J. Virol. 77: 11674-11684 [Abstract] [Full Text]  
• Cumming, S. A., McPhillips, M. G., Veerapraditsin, T., Milligan, S. G., Graham, S. V. (2003). Activity of the Human Papillomavirus Type 16 Late Negative Regulatory Element Is Partly due to Four Weak Consensus 5' Splice Sites That Bind a U1 snRNP-Like Complex. J. Virol. 77: 5167-5177 [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]  
• Cumming, S. A., Repellin, C. E., McPhillips, M., Radford, J. C., Clements, J. B., Graham, S. V. (2002). The Human Papillomavirus Type 31 Late 3' Untranslated Region Contains a Complex Bipartite Negative Regulatory Element. J. Virol. 76: 5993-6003 [Abstract] [Full Text]  
• Collier, B., Oberg, D., Zhao, X., Schwartz, S. (2002). Specific Inactivation of Inhibitory Sequences in the 5' End of the Human Papillomavirus Type 16 L1 Open Reading Frame Results in Production of High Levels of L1 Protein in Human Epithelial Cells. J. Virol. 76: 2739-2752 [Abstract] [Full Text]  
• Leder, C., Kleinschmidt, J. A., Wiethe, C., Muller, M. (2001). Enhancement of Capsid Gene Expression: Preparing the Human Papillomavirus Type 16 Major Structural Gene L1 for DNA Vaccination Purposes. J. Virol. 75: 9201-9209 [Abstract] [Full Text]  
• Spångberg, K., Wiklund, L., Schwartz, S. (2001). Binding of the La autoantigen to the hepatitis C virus 3' untranslated region protects the RNA from rapid degradation in vitro. J. Gen. Virol. 82: 113-120 [Abstract] [Full Text]  
• Dolei, A., Curreli, S., Marongiu, P., Pierangeli, A., Gomes, E., Bucci, M., Serra, C., Degener, A. M. (1999). Human immunodeficiency virus infection in vitro activates naturally integrated human papillomavirus type 18 and induces synthesis of the L1 capsid protein. J. Gen. Virol. 80: 2937-2944 [Abstract] [Full Text]  
• Terhune, S. S., Milcarek, C., Laimins, L. A. (1999). Regulation of Human Papillomavirus Type 31 Polyadenylation during the Differentiation-Dependent Life Cycle. J. Virol. 73: 7185-7192 [Abstract] [Full Text]  
• Sokolowski, M., Furneaux, H., Schwartz, S. (1999). The Inhibitory Activity of the AU-Rich RNA Element in the Human Papillomavirus Type 1 Late 3' Untranslated Region Correlates with Its Affinity for the elav-Like HuR Protein. J. Virol. 73: 1080-1091 [Abstract] [Full Text]  
• Collier, B., Goobar-Larsson, L., Sokolowski, M., Schwartz, S. (1998). Translational Inhibition in Vitro of Human Papillomavirus Type 16 L2 mRNA Mediated through Interaction with Heterogenous Ribonucleoprotein K and Poly(rC)-binding Proteins 1 and 2. J. Biol. Chem. 273: 22648-22656 [Abstract] [Full Text]  
• Sokolowski, M., Tan, W., Jellne, M., Schwartz, S. (1998). mRNA Instability Elements in the Human Papillomavirus Type 16 L2 Coding Region. J. Virol. 72: 1504-1515 [Abstract] [Full Text]  
• Dietrich-Goetz, W., Kennedy, I. M., Levins, B., Stanley, M. A., Clements, J. B. (1997). A cellular 65-kDa protein recognizes the negative regulatory element of human papillomavirus late mRNA. Proc. Natl. Acad. Sci. USA 94: 163-168 [Abstract] [Full Text]