CONTROL OF PAPILLOMAVIRUS LATE GENE EXPRESSION

乳头状病毒晚期基因表达的控制

• 批准号: 5201496
• 负责人: C C BAKER
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201496
• 关键词: RNA splicing; bovine papillomavirus; cell differentiation; gene expression; genetic regulatory element; in situ hybridization; messenger RNA; microorganism culture; neoplasm /cancer genetics; nucleic acid sequence; polyadenylate; transcription factor; transfection; transfection /expression vector; virus RNA; virus genetics; virus protein

The papillomaviruses are small DNA tumor viruses which cause benign and malignant lesions of squamous epithelia in higher vertebrates. The complete lytic cycle of these viruses occurs only in the differentiated keratinocytes of a squamous epithelium. Bovine papillomavirus type 1 (BPV-1) was used as a model system for the study of the regulation of papillomavirus gene expression by keratinocyte differentiation. In situ hybridization studies using sections of bovine fibropapillomas and mRNA specific oligonucleotide probes demonstrated that the splicing of BPV-1 late pre-mRNAs is regulated in a differentiation specific manner. Other posttranscriptional regulatory mechanisms also control late gene expression. Sequences in the 5' untranslated regions (UTR) of the BPV-1 major capsid protein (L1) mRNA have been shown to affect translation of this protein. In addition, a cis-acting regulatory element which inhibits late gene expression has been identified in the late 3' UTR of BPV-1 and human papillomavirus type 16 (HPV-16). This element has been characterized as a 5' splice site and shown to bind the splicing factor U1 snRNP. The function of this element appears to be inhibition of polyadenylation rather than splicing, however. The activity of this element was shown to be blocked by the human immunodeficiency type 1 (HIV-1) Rev protein, raising the possibility that viral and/or cellular Rev-like proteins may control the activity of the papillomavirus late 3'UTR elements. A nonconsensus 5' splice site in the BPV-1 early region has also been shown to be important in the regulation of early versus late poly(A) site choice. This system was used to further investigate the mechanism of inhibition of gene expression by 5' splice sites. Using in vivo transfection experiments and competition with a cis- acting hammerhead ribozyme, a consensus 5' splice site was shown to inhibit polyadenylation. Furthermore, a 5' splice site had no effect on an alternative mechanism of mRNA 3' end formation used by histone mRNAs or on nucleocytoplasmic transport of mRNAs processed by histone 3' end formation, demonstrating the specificity of this interaction.

乳头瘤病毒是一种小的DNA肿瘤病毒，它能引起良性和 高等脊椎动物鳞状上皮的恶性病变。这个 这些病毒的完整裂解周期只发生在分化的 鳞状上皮的角质形成细胞。牛乳头瘤病毒1型 (BPV-1)作为模型系统，用于研究生物大分子的调控。 角质形成细胞分化过程中乳头瘤病毒基因的表达。就地 牛纤维乳头状瘤组织切片与mRNA的杂交研究 特异的寡核苷酸探针证明BPV-1的剪接 晚期Pre-mRNAs以分化特异性的方式调节。其他 转录后调控机制也控制晚期基因 表情。BPV-1基因5‘非翻译区的序列分析 主要衣壳蛋白(L1)的mRNA已被证明影响翻译 这种蛋白质。此外，顺式作用的调节元件 抑制晚期基因表达已被发现存在于晚期3‘非编码区。 BPV-1和人类乳头瘤病毒16型(HPV-16)。这一元素一直是 以5‘剪接位点为特征，并显示与剪接因子结合 U1单链RNP。这一元素的功能似乎是抑制 然而，聚腺苷酸化而不是剪接。这个活动的活动 该元件被人类免疫缺陷1型所阻断。 (HIV-1)Rev蛋白，增加了病毒和/或细胞 REV样蛋白可能控制晚期乳头瘤病毒的活性 3‘非编码区单元。BPV-1早期区域的一个非共识5‘剪接位点 也被证明在调节早期和 最近的保利(A)选址。该系统被用来进一步研究 5‘剪接位点抑制基因表达的机制。vbl.使用 体内转基因实验及其与顺式作用的竞争 锤头状核酶，一个共识的5‘剪接位点被证明抑制 多聚腺苷酸化。此外，5‘剪接位点对 组蛋白mRNAs或mRNA3‘末端形成的替代机制 组蛋白3‘端处理的mRNAs核质转运的研究 形成，证明了这种相互作用的特殊性。