Previous Article | Next Article 
Journal of Virology, February 1999, p. 1080-1091, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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
Marcus
Sokolowski,1
Henry
Furneaux,2 and
Stefan
Schwartz1,*
Department of Medical Biochemistry and
Microbiology, Biomedical Center, Uppsala University, 751 23 Uppsala,
Sweden,1 and
Program in Molecular
Pharmacology and Therapeutics, Memorial Sloan Kettering Cancer
Center, New York, New York 100212
Received 19 August 1998/Accepted 2 November 1998
A 57-nucleotide adenosine- and uridine-rich RNA instability element
in the human papillomavirus type 1 late 3' untranslated region termed
h1ARE has previously been shown to interact specifically with three nuclear proteins that failed to bind to an inactive mutant
RNA. Two of those were identified as the heterogeneous ribonucleoproteins C1 and C2, whereas the third, a 38-kDa, poly(U) binding protein (p38), remained unidentified. Here we show that partially purified p38 reacts with a monoclonal antibody raised against
the recently identified elav-like HuR protein, indicating that p38 is
the HuR protein. Indeed, recombinant glutathione
S-transferase (GST)-HuR protein binds specifically to sites
within the h1ARE. Determination of the apparent
Kd value of GST-HuR for the h1ARE and the inactive mutant thereof revealed that GST-HuR bound with a more
than 50-fold-higher affinity to the wild-type sequence. Therefore, the
binding affinity of GST-HuR for the wild-type and mutant
h1AREs correlates with their inhibitory activities in
transfected cells, strongly suggesting that the HuR protein is involved
in the posttranscriptional regulation of human papillomavirus type 1 late-gene expression.
*
Corresponding author. Mailing address: Department of
Medical Biochemistry and Microbiology, Biomedical Center, Uppsala
University, Husargatan 3, Box 582, 751 23 Uppsala, Sweden. Phone: 4618 471 4239. Fax: 4618 509 876. E-mail:
Stefan.Schwartz{at}imim.uu.se.
Journal of Virology, February 1999, p. 1080-1091, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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]
-
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]
-
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]
-
Giles, K. M., Daly, J. M., Beveridge, D. J., Thomson, A. M., Voon, D. C., Furneaux, H. M., Jazayeri, J. A., Leedman, P. J.
(2003). The 3'-Untranslated Region of p21WAF1 mRNA Is a Composite cis-Acting Sequence Bound by RNA-binding Proteins from Breast Cancer Cells, Including HuR and Poly(C)-binding Protein. J. Biol. Chem.
278: 2937-2946
[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]
-
Goldberg-Cohen, I., Furneauxb, H., Levy, A. P.
(2002). A 40-bp RNA Element That Mediates Stabilization of Vascular Endothelial Growth Factor mRNA by HuR. J. Biol. Chem.
277: 13635-13640
[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]
-
Lisbin, M. J., Qiu, J., White, K.
(2001). The neuron-specific RNA-binding protein ELAV regulates neuroglian alternative splicing in neurons and binds directly to its pre-mRNA. Genes Dev.
15: 2546-2561
[Abstract]
[Full Text]
-
Sheflin, L. G., Zhang, W., Spaulding, S. W.
(2001). Androgen Regulates the Level and Subcellular Distribution of the AU-Rich Ribonucleic Acid-Binding Protein HuR Both in Vitroand in Vivo. Endocrinology
142: 2361-2368
[Abstract]
[Full Text]
-
Anderson, P.
(2000). Post-transcriptional regulation of tumour necrosis factor alpha production. Ann Rheum Dis
59: i3-5
[Full Text]
-
Lisbin, M. J., Gordon, M., Yannoni, Y. M., White, K.
(2000). Function of RRM Domains of Drosophila melanogaster ELAV: RNP1 Mutations and RRM Domain Replacements With ELAV Family Proteins and SXL. Genetics
155: 1789-1798
[Abstract]
[Full Text]
-
Di Noia, J. M., D'Orso, I., Sanchez, D. O., Frasch, A. C. C.
(2000). AU-rich Elements in the 3'-Untranslated Region of a New Mucin-type Gene Family of Trypanosoma cruzi Confers mRNA Instability and Modulates Translation Efficiency. J. Biol. Chem.
275: 10218-10227
[Abstract]
[Full Text]
-
Rodriguez-Pascual, F., Hausding, M., Ihrig-Biedert, I., Furneaux, H., Levy, A. P., Forstermann, U., Kleinert, H.
(2000). Complex Contribution of the 3'-Untranslated Region to the Expressional Regulation of the Human Inducible Nitric-oxide Synthase Gene. INVOLVEMENT OF THE RNA-BINDING PROTEIN HuR. J. Biol. Chem.
275: 26040-26049
[Abstract]
[Full Text]