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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.


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