Inhibition of translation by UAUUUAU and UAUUUUUAU motifs of the AU-rich RNA instability element in the HPV-1 late 3' untranslated region.
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.
Wiklund
Lisa
L
Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Husargatan 3, Box 582, 751 23 Uppsala, Sweden.
Sokolowski
Marcus
M
Carlsson
Anette
A
Rush
Margaret
M
Schwartz
Stefan
S
D020413:3' Untranslated Regions; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D013006:Growth Hormone / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis
D020413:3' Untranslated Regions; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; D014764:Viral Proteins; D013006:Growth Hormone; D015500:Chloramphenicol O-Acetyltransferase