Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
Virus Res. 2010 May;149(2):217-23. doi: 10.1016/j.virusres.2010.02.001. Epub 2010 Feb 8.
All human papillomavirus type 16 (HPV-16) early mRNAs are polyadenylated at the poly(A) signal within the early 3' untranslated region (3'UTR). The 3'end of the early E5 open reading frame and the 3'UTR of HPV-16 is very AU-rich, with five regions similar to cytoplasmic polyadenylation elements (CPEs). We show here that a fragment of the early 3'end comprising four of the five CPE-like regions when inserted downstream of a reporter gene confers regulation of the gene expression. A key protein involved in cytoplasmic polyadenylation is CPEB. We show that the human CPEB1 can repress the activity of the reporter construct containing the HPV-16 early sequences. This repression can be counteracted by a human cytoplasmic poly(A) polymerase, hGLD-2 fused to CPEB1. The hGLD-2/CPEB1 fusion protein facilitates furthermore poly(A) elongation of early HPV transcripts.
所有人类乳头瘤病毒 16 型(HPV-16)早期 mRNA 都在早期 3'非翻译区(3'UTR)内的 poly(A)信号处多聚腺苷酸化。早期 E5 开放阅读框的 3'端和 HPV-16 的 3'UTR 富含 AU,有五个类似于细胞质多聚腺苷酸化元件(CPE)的区域。我们在这里表明,当包含五个 CPE 样区域中的四个的早期 3'端片段插入报告基因的下游时,该基因可以调节基因表达。参与细胞质多聚腺苷酸化的关键蛋白是 CPEB。我们表明,人 CPEB1 可以抑制含有 HPV-16 早期序列的报告构建体的活性。这种抑制可以被与人细胞质多聚(A)聚合酶 hGLD-2 融合的 CPEB1 逆转。hGLD-2/CPEB1 融合蛋白还促进了早期 HPV 转录物的 poly(A)延伸。