Schwartz Stefan
Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, Uppsala, Sweden.
Front Biosci. 2008 May 1;13:5880-91. doi: 10.2741/3123.
To understand human papillomavirus type 16 (HPV-16) gene regulation, it is necessary to understand HPV-16 RNA processing. HPV-16 encodes multiple 5'- and 3'-splice sites and two polyadenylation signals pAE and pAL (Figure 1). The major 3'-splice site on the HPV-16 genome (SA3358) is used for generation of E6, E7, E4, L1 and L2 mRNAs. It encodes a suboptimal splice signal but is under control of a strong enhancer that renders SA3358 one of the most efficiently used splice sites on the HPV-16 genome. Thereby SA3358 indirectly blocks HPV-16 late gene expression. The early polyA signal is also under control of the early UTR sequence and multiple RNA elements in the L2 coding region that interact with hnRNP H. The two splice sites SD3632 and SA5639 are used exclusively by late mRNAs and are under control of multiple splicing silencer elements. The silencers at SA5639 are located in the L1 coding region and interact with hnRNP A1. So far, only polypyrimidine tract binding protein (PTB) has been shown to induce late gene expression.
为了解人乳头瘤病毒16型（HPV - 16）的基因调控，有必要了解HPV - 16的RNA加工过程。HPV - 16编码多个5'和3'剪接位点以及两个聚腺苷酸化信号pAE和pAL（图1）。HPV - 16基因组上的主要3'剪接位点（SA3358）用于生成E6、E7、E4、L1和L2 mRNA。它编码一个次优剪接信号，但受一个强增强子的控制，这使得SA3358成为HPV - 16基因组上最有效使用的剪接位点之一。由此SA3358间接阻断HPV - 16晚期基因表达。早期聚腺苷酸化信号也受早期非翻译区序列以及L2编码区中与hnRNP H相互作用的多个RNA元件的控制。两个剪接位点SD3632和SA5639仅被晚期mRNA使用，并受多个剪接沉默子元件的控制。SA5639处的沉默子位于L1编码区并与hnRNP A1相互作用。到目前为止，只有多嘧啶序列结合蛋白（PTB）已被证明可诱导晚期基因表达。
