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 Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Furth, P A Articles by Baker, C C Search for Related Content PubMed PubMed Citation Articles by Furth, P A Articles by Baker, C C

Sequences homologous to 5' splice sites are required for the inhibitory activity of papillomavirus late 3' untranslated regions.

Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.

ABSTRACT

Expression of bovine papillomavirus type 1 (BPV-1) late genes is limited to terminally differentiated keratinocytes in an infected epithelium. We have previously shown that although the BPV-1 late polyadenylation site is functional in nonpermissive cells, a 53-nucleotide (nt) fragment of the late 3' untranslated region acts posttranscriptionally to reduce polyadenylated cytoplasmic RNA levels. This 53-nt fragment does not appear to function by destabilizing polyadenylated cytoplasmic RNA (P. A. Furth and C. C. Baker, J. Virol. 65:5806-5812, 1991). In this study, we used site-directed mutagenesis and deletion analysis to demonstrate that the sequence AAG/GUAAGU, which is identical to the consensus 5' splice site sequence, was both necessary and sufficient for the inhibitory activity of the 53-nt fragment. Furthermore, base pairing between the 5' end of the U1 small nuclear RNA and this 5' splice site-like sequence was shown to be required for the inhibitory activity in vivo. We have also further mapped the human papillomavirus type 16 late 3' inhibitory element (I. M. Kennedy, J. K. Haddow, and J. B. Clements, J. Virol. 65:2093-2097, 1991) to a 51-nt region containing four overlapping sequence motifs with partial homology to 5' splice sites. Mutation of each of these motifs demonstrated that only one of these motifs is required for the inhibitory activity. However, the presence of the other motifs may contribute to the full inhibitory activity of the element. No BPV-1 or human papillomavirus type 16 mRNAs which are spliced by using the potential 5' splice sites present in the viral late 3' untranslated regions have been identified. This suggests that the primary function of these 5' splice site-like sequences is the inhibition of late gene expression. The most likely mechanism of action of these elements is reduction of polyadenylation efficiency, perhaps through interference with 3'-terminal exon definition.

This article has been cited by other articles:

• Abad, X., Vera, M., Jung, S. P., Oswald, E., Romero, I., Amin, V., Fortes, P., Gunderson, S. I. (2008). Requirements for gene silencing mediated by U1 snRNA binding to a target sequence. Nucleic Acids Res 36: 2338-2352 [Abstract] [Full Text]  
• Goraczniak, R., Gunderson, S. I. (2008). The Regulatory Element in the 3'-Untranslated Region of Human Papillomavirus 16 Inhibits Expression by Binding CUG-binding Protein 1. J. Biol. Chem. 283: 2286-2296 [Abstract] [Full Text]  
• Guan, F., Caratozzolo, R. M., Goraczniak, R., Ho, E. S., Gunderson, S. I. (2007). A bipartite U1 site represses U1A expression by synergizing with PIE to inhibit nuclear polyadenylation. RNA 13: 2129-2140 [Abstract] [Full Text]  
• Qiu, J., Cheng, F., Pintel, D. (2007). Distance-Dependent Processing of Adeno-Associated Virus Type 5 RNA Is Controlled by 5' Exon Definition. J. Virol. 81: 7974-7984 [Abstract] [Full Text]  
• Sajic, R., Lee, K., Asai, K., Sakac, D., Branch, D. R., Upton, C., Cochrane, A. (2007). Use of modified U1 snRNAs to inhibit HIV-1 replication. Nucleic Acids Res 35: 247-255 [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]  
• Berg, M., DiFatta, J., Hoiczyk, E., Schlegel, R., Ketner, G. (2005). Viable adenovirus vaccine prototypes: High-level production of a papillomavirus capsid antigen from the major late transcriptional unit. Proc. Natl. Acad. Sci. USA 102: 4590-4595 [Abstract] [Full Text]  
• Adair, R., Liebisch, G. W., Su, Y., Colberg-Poley, A. M. (2004). Alteration of cellular RNA splicing and polyadenylation machineries during productive human cytomegalovirus infection. J. Gen. Virol. 85: 3541-3553 [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]  
• McPhillips, M. G., Veerapraditsin, T., Cumming, S. A., Karali, D., Milligan, S. G., Boner, W., Morgan, I. M., Graham, S. V. (2004). SF2/ASF Binds the Human Papillomavirus Type 16 Late RNA Control Element and Is Regulated during Differentiation of Virus-Infected Epithelial Cells. J. Virol. 78: 10598-10605 [Abstract] [Full Text]  
• Osipovich, A. B., White-Grindley, E. K., Hicks, G. G., Roshon, M. J., Shaffer, C., Moore, J. H., Ruley, H. E. (2004). Activation of cryptic 3' splice sites within introns of cellular genes following gene entrapment. Nucleic Acids Res 32: 2912-2924 [Abstract] [Full Text]  
• Qiu, J., Pintel, D. J. (2004). Alternative Polyadenylation of Adeno-associated Virus Type 5 RNA within an Internal Intron Is Governed by the Distance between the Promoter and the Intron and Is Inhibited by U1 Small Nuclear RNP Binding to the Intervening Donor. J. Biol. Chem. 279: 14889-14898 [Abstract] [Full Text]  
• Liu, P., Kronenberg, M., Jiang, X., Rowe, D. (2004). Modified U1 snRNA suppresses expression of a targeted endogenous RNA by inhibiting polyadenylation of the transcript. Nucleic Acids Res 32: 1512-1517 [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]  
• Qiu, J., Nayak, R., Pintel, D. J. (2004). Alternative Polyadenylation of Adeno-Associated Virus Type 5 RNA within an Internal Intron Is Governed by both a Downstream Element within the Intron 3' Splice Acceptor and an Element Upstream of the P41 Initiation Site. J. Virol. 78: 83-93 [Abstract] [Full Text]  
• Su, Y., Adair, R., Davis, C. N., DiFronzo, N. L., Colberg-Poley, A. M. (2003). Convergence of RNA cis Elements and Cellular Polyadenylation Factors in the Regulation of Human Cytomegalovirus UL37 Exon 1 Unspliced RNA Production. J. Virol. 77: 12729-12741 [Abstract] [Full Text]  
• Fortes, P., Cuevas, Y., Guan, F., Liu, P., Pentlicky, S., Jung, S. P., Martinez-Chantar, M. L., Prieto, J., Rowe, D., Gunderson, S. I. (2003). Inhibiting expression of specific genes in mammalian cells with 5' end-mutated U1 small nuclear RNAs targeted to terminal exons of pre-mRNA. Proc. Natl. Acad. Sci. USA 100: 8264-8269 [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]  
• Aissouni, Y., Perez, C., Calmels, B., Benech, P. D. (2002). The Cleavage/Polyadenylation Activity Triggered by a U-rich Motif Sequence Is Differently Required Depending on the Poly(A) Site Location at Either the First or Last 3'-Terminal Exon of the 2'-5' Oligo(A) Synthetase Gene. J. Biol. Chem. 277: 35808-35814 [Abstract] [Full Text]  
• Liu, P., Gucwa, A., Stover, M. L., Buck, E., Lichtler, A., Rowe, D. (2002). Analysis of inhibitory action of modified U1 snRNAs on target gene expression: discrimination of two RNA targets differing by a 1 bp mismatch. Nucleic Acids Res 30: 2329-2339 [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]  
• Terhune, S. S., Hubert, W. G., Thomas, J. T., Laimins, L. A. (2001). Early Polyadenylation Signals of Human Papillomavirus Type 31 Negatively Regulate Capsid Gene Expression. J. Virol. 75: 8147-8157 [Abstract] [Full Text]  
• Beckley, S. A., Liu, P., Stover, M. L., Gunderson, S. I., Lichtler, A. C., Rowe, D. W. (2001). Reduction of Target Gene Expression by a Modified U1 snRNA. Mol. Cell. Biol. 21: 2815-2825 [Abstract] [Full Text]  
• McCullough, A. J., Berget, S. M. (2000). An Intronic Splicing Enhancer Binds U1 snRNPs To Enhance Splicing and Select 5' Splice Sites. Mol. Cell. Biol. 20: 9225-9235 [Abstract] [Full Text]  
• Cooke, C., Hans, H., Alwine, J. C. (1999). Utilization of Splicing Elements and Polyadenylation Signal Elements in the Coupling of Polyadenylation and Last-Intron Removal. Mol. Cell. Biol. 19: 4971-4979 [Abstract] [Full Text]  
• Zhou, J., Liu, W. J., Peng, S. W., Sun, X. Y., Frazer, I. (1999). Papillomavirus Capsid Protein Expression Level Depends on the Match between Codon Usage and tRNA Availability. J. Virol. 73: 4972-4982 [Abstract] [Full Text]  
• Zhao, J., Hyman, L., Moore, C. (1999). Formation of mRNA 3' Ends in Eukaryotes: Mechanism, Regulation, and Interrelationships with Other Steps in mRNA Synthesis. Microbiol. Mol. Biol. Rev. 63: 405-445 [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]  
• Lou, H., Neugebauer, K. M., Gagel, R. F., Berget, S. M. (1998). Regulation of Alternative Polyadenylation by U1 snRNPs and SRp20. Mol. Cell. Biol. 18: 4977-4985 [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]  
• Moreira, A., Takagaki, Y., Brackenridge, S., Wollerton, M., Manley, J. L., Proudfoot, N. J. (1998). The upstream sequence element of the C2 complement poly(A) signal activates mRNA 3' end formation by two distinct mechanisms. Genes Dev. 12: 2522-2534 [Abstract] [Full Text]  
• Tan, S.-H., Bartsch, D., Schwarz, E., Bernard, H.-U. (1998). Nuclear Matrix Attachment Regions of Human Papillomavirus Type 16 Point toward Conservation of These Genomic Elements in All Genital Papillomaviruses. J. Virol. 72: 3610-3622 [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]  
• Colgan, D. F., Manley, J. L. (1997). Mechanism and regulation of mRNA polyadenylation. Genes Dev. 11: 2755-2766 [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]  
• Ashe, M P, Griffin, P, James, W, Proudfoot, N J (1995). Poly(A) site selection in the HIV-1 provirus: inhibition of promoter-proximal polyadenylation by the downstream major splice donor site.. Genes Dev. 9: 3008-3025 [Abstract]  
• Koffa, M. D., Graham, S. V., Takagaki, Y., Manley, J. L., Clements, J. B. (2000). The human papillomavirus type 16 negative regulatory RNA element interacts with three proteins that act at different posttranscriptional levels. Proc. Natl. Acad. Sci. USA 97: 4677-4682 [Abstract] [Full Text]