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

Citation
M. Sokolowski et al., 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 VIROLOGY, 73(2), 1999, pp. 1080-1091
Citations number
54
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Microbiology
Journal title
JOURNAL OF VIROLOGY
ISSN journal
0022-538X → ACNP
Volume
73
Issue
2
Year of publication
1999
Pages
1080 - 1091
Database
ISI
SICI code
0022-538X(199902)73:2<1080:TIAOTA>2.0.ZU;2-I
Abstract
A 57-nucleotide adenosine- and uridine-rich RNA instability element in the human papillomavirus type 1 late 3' untranslated region termed h1ARE has pr eviously been shown to interact specifically with three nuclear proteins th at failed to bind to an inactive mutant RNA. Two of those were identified a s the heterogeneous ribonucleoproteins C1 and C2, whereas the third, a 38-k Da, poly(U) binding protein (p38), remained unidentified. Here we! show tha t partially purified p38 reacts with a monoclonal antibody raised against t he recently identified elav-like HuR protein, indicating that p38 is the Hu R protein. Indeed, recombinant glutathione S-transferase (GST)-HuR protein binds specifically to sites within the WARE. Determination of the apparent K-d 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-ty pe sequence. Therefore, the binding affinity of GST-HuR for the wild-type a nd mutant h1AREs correlates with their inhibitory activities in transfected cells, strongly suggesting that the HuR protein is involved in the posttra nscriptional regulation of human papillomavirus type 1 late-gene expression .