CONTROL OF PAPILLOMAVIRUS LATE TRANSCRIPTION

乳头状病毒晚期转录的控制

• 批准号: 3752665
• 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/3752665
• 关键词: RNA splicing; bovine papillomavirus; cell differentiation; gene expression; gene mutation; genetic models; genetic promoter element; genetic regulation; genetic regulatory element; genetic transcription; host organism interaction; human immunodeficiency virus 1; in situ hybridization; keratinocyte; messenger RNA; microorganism culture; neoplasm /cancer genetics; nucleic acid sequence; polyadenylate; posttranscriptional RNA processing; small nuclear RNA; transcription factor; transfection; transfection /expression vector; virus RNA; virus genetics; virus protein; virus replication; warts

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 papillomavirusus 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 mRNA specific probes have demonstrated that this regulation is both transcriptional and posttranscriptional. Transfection studies using mini-late transcription unit expression vectors have demonstrated that RNA processing changes which occur in the granular layer of the wart are essential for the early to late shift in viral expression. A cis-acting regulatory element which inhibits BPV-1 late gene expression has been identified in the late 3' untranslated region (UTR). Mutational analysis of this element indicated that a consensus 5' splice site sequence is essential for its function. In addition, base pairing between this element and the U1 smRNA, which normally base pairs with 5' splice sites during splicing, is necessary for the activity of the element. This element, however, does not appear to be used for splicing and most likely functions by inhibiting polyadenylation at the late poly(A) site. A similar inhibitory element has also been identified in the HPV-16 late 3' UTR. The HIV-1 Rev protein, which interacts with cellular splicing machinery to facilitate the nucleocytoplasmid transport of unspliced HIV mRNAs, was able to reverse the effects of the BPV-1 3' UTR element on expression from a vector which also contained a Rev binding site (RRE). This suggests that the activity of the 3' UTR element could be regulated by a viral or cellular Rev-like protein.

乳头瘤病毒是小型 DNA 肿瘤病毒，可引起良性和 高等脊椎动物鳞状上皮的恶性病变。 这 这些病毒的完整裂解周期仅发生在分化的细胞中 鳞状上皮的角质形成细胞。 牛乳头瘤病毒1型 （BPV-1）被用作模型系统来研究调节 通过角质形成细胞分化表达乳头瘤病毒基因。 原位 使用 mRNA 特异性探针的杂交研究表明 这种调节既是转录的又是转录后的。 使用微型晚期转录单元表达的转染研究 载体已经证明，RNA 加工过程的变化发生在 疣的颗粒层对于疣的早期到晚期的转变至关重要 病毒表达。 抑制 BPV-1 的顺式作用调节元件 晚期基因表达已在晚期 3' 未翻译中被鉴定 区域（UTR）。 该元素的突变分析表明 共有 5' 剪接位点序列对其功能至关重要。 在 此外，该元件与 U1 smRNA 之间的碱基配对， 通常在剪接过程中需要有 5' 剪接位点的碱基对 为元素的活动。 然而这个元素并没有出现 通过抑制用于剪接和最可能的功能 晚期聚（A）位点的聚腺苷酸化。 类似的抑制元素 HPV-16 晚期 3' UTR 中也已被鉴定。 HIV-1 修订版 蛋白质，它与细胞剪接机器相互作用以促进 未剪接的 HIV mRNA 的核细胞质转运 逆转 BPV-1 3' UTR 元件对表达的影响 还包含 Rev 结合位点 (RRE) 的载体。 这表明 3' UTR 元件的活性可以通过病毒或 细胞 Rev 样蛋白。