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 Zhao, X.
Right arrow Articles by Schwartz, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, X.
Right arrow Articles by Schwartz, S.

 Previous Article  |  Next Article 

Journal of Virology, April 2005, p. 4270-4288, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4270-4288.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Xiaomin Zhao,1 Daniel Öberg,1 Margaret Rush,1 Joanna Fay,2 Helen Lambkin,2 and Stefan Schwartz1*

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden,1 Dublin Institute of Technology, Dublin, Ireland2

Received 18 August 2004/ Accepted 15 November 2004

We have investigated the role of the human papillomavirus type 16 (HPV-16) early untranslated region (3' UTR) in HPV-16 gene expression. We found that deletion of the early 3' UTR reduced the utilization of the early polyadenylation signal and, as a consequence, resulted in read-through into the late region and production of late L1 and L2 mRNAs. Deletion of the U-rich 3' half of the early 3' UTR had a similar effect, demonstrating that the 57-nucleotide U-rich region acted as an enhancing upstream element on the early polyadenylation signal. In accordance with this, the newly identified hFip1 protein, which has been shown to enhance polyadenylation through U-rich upstream elements, interacted specifically with the HPV-16 upstream element. This upstream element also interacted specifically with CstF-64, hnRNP C1/C2, and polypyrimidine tract binding protein, suggesting that these factors were either enhancing or regulating polyadenylation at the HPV-16 early polyadenylation signal. Mutational inactivation of the early polyadenylation signal also resulted in increased late mRNA production. However, the effect was reduced by the activation of upstream cryptic polyadenylation signals, demonstrating the presence of additional strong RNA elements downstream of the early polyadenylation signal that direct cleavage and polyadenylation to this region of the HPV-16 genome. In addition, we identified a 3' splice site at genomic position 742 in the early region with the potential to produce E1 and E4 mRNAs on which the E1 and E4 open reading frames are preceded only by the suboptimal E6 AUG. These mRNAs would therefore be more efficiently translated into E1 and E4 than previously described HPV-16 E1 and E4 mRNAs on which E1 and E4 are preceded by both E6 and E7 AUGs.

* Corresponding author. Mailing address: Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, Box 582, Husargatan 3, 751 23 Uppsala, Sweden. Phone: 4618 471 4239 4618 471 4322. Fax: 4618 509 876. E-mail: Stefan.Schwartz{at}imbim.uu.se.

Journal of Virology, April 2005, p. 4270-4288, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4270-4288.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mole, S., Milligan, S. G., Graham, S. V. (2009). Human Papillomavirus Type 16 E2 Protein Transcriptionally Activates the Promoter of a Key Cellular Splicing Factor, SF2/ASF. J. Virol. 83: 357-367 [Abstract] [Full Text]  
  • 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]  
  • Gu, W., Ding, J., Wang, X., de Kluyver, R. L., Saunders, N. A., Frazer, I. H., Zhao, K.-N. (2007). Generalized substitution of isoencoding codons shortens the duration of papillomavirus L1 protein expression in transiently gene-transfected keratinocytes due to cell differentiation. Nucleic Acids Res 0: gkm496v1-13 [Abstract] [Full Text]  
  • Hall-Pogar, T., Liang, S., Hague, L. K., Lutz, C. S. (2007). Specific trans-acting proteins interact with auxiliary RNA polyadenylation elements in the COX-2 3'-UTR. RNA 13: 1103-1115 [Abstract] [Full Text]  
  • Dalziel, M., Nunes, N. M., Furger, A. (2007). Two G-Rich Regulatory Elements Located Adjacent to and 440 Nucleotides Downstream of the Core Poly(A) Site of the Intronless Melanocortin Receptor 1 Gene Are Critical for Efficient 3' End Processing. Mol. Cell. Biol. 27: 1568-1580 [Abstract] [Full Text]  
  • Zhu, H., Zhou, H.-L., Hasman, R. A., Lou, H. (2007). Hu Proteins Regulate Polyadenylation by Blocking Sites Containing U-rich Sequences. J. Biol. Chem. 282: 2203-2210 [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]  


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