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J. Biol. Chem., Vol. 277, Issue 43, 40462-40471, October 25, 2002
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From the Department of Medical Biochemistry and Microbiology,
Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden
The human papillomavirus type 1 (HPV-1) late
mRNAs contain a 57-nucleotide adenosine- and uridine-rich RNA
instability element termed h1ARE in their late 3' untranslated regions.
Here we show that five sequence motifs in the h1ARE (named I-V) affect
the mRNA half-life in an additive manner. The minimal inhibitory
sequence in motifs I and II was mapped to UAUUUAU, and the minimal
inhibitory sequence in motifs III-V was mapped to UAUUUUUAU. We also
provide evidence that the same motifs in the AU-RNA instability element inhibit mRNA translation, an effect that was entirely dependent on
the presence of a poly(A) tail on the mRNA. Additional experiments demonstrated that the h1ARE interacted directly with the
poly(A)-binding protein, suggesting that the h1ARE inhibits translation
by interfering with the function of the poly(A)-binding protein.
Inhibition of Translation by UAUUUAU and UAUUUUUAU Motifs of the
AU-rich RNA Instability Element in the HPV-1 Late 3' Untranslated
Region*
,
*
This work was supported by the Swedish Medical Research
Council, the Swedish Cancer Society, and the Swedish Society for
Medical Research.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Received a fellowship from the Emil and Ragna Börjessons Minnesfond.
§
To whom correspondence should be addressed: Dept. of Medical
Biochemistry and Microbiology, Biomedical Center, Uppsala University, Husargatan 3, Box 582, 751 23 Uppsala, Sweden. Tel.: 4618-471-4239; Fax: 4618-509-876; E-mail: Stefan.Schwartz@imbim.uu.se.
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