CONTROL OF PAPILLOMAVIRUS LATE TRANSCRIPTION

乳头状病毒晚期转录的控制

• 批准号: 3838380
• 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/3838380
• 关键词: RNA splicing; bovine papillomavirus; gene expression; genetic models; genetic regulation; genetic regulatory element; genetic transcription; mutant; polyadenylate; posttranscriptional RNA processing; transfection /expression vector; virus genetics; virus replication

The papillomaviruses cause benign and malignant lesions of squamous epithelia in higher vertebrates. The complete lytic cycle of these viruses (including late gene expression) occurs only in the differentiated cells of the squamous epithelium. Malignant lesions and infected cells in culture do not produce virus. Bovine papillomavirus type 1 (BPV-1) was used as a model system for the study of papillomavirus late gene expression and its control. The data suggest that late gene expression is regulated at multiple transcriptional and post-transcriptional levels. BPV-1 mutants as well as eukaryotic expression vectors have been used to show that the BPV-1 late polyadenylation site can be efficiently utilized, even in transformed cells, and that the late poly(A) site is a more efficient poly(A) site than the early poly(A) site. The inefficient use of the late poly(A) site in its normal context may be due partially to transcriptional pausing between the early and late poly(A) sites in transformed cells and partially to a short inhibitory element in the late 3' UTR. This late 3' UTR element was shown not to function by destabilizing late mRNAs and may function at an RNA processing or transport level. There is also evidence that the BPV-1 poly(A) site choice may be regulated by splicing factors. Current data suggest that utilization of an alternative splice acceptor at nt 3225 coupled with enhanced recognition of a weak nonconsensus splice donor at nt 3764 are critical events in the early to late shift. It was shown, using a late minigene expression vector driven by a heterologous promoter, that mutation of the nt 3225 splice acceptor, forcing use of the nt 3605 splice acceptor, mutation of the nt 3764 splice donor to a strong consensus sequence, and vegetative replication are both necessary and sufficient to give a late pattern of RNA processing. Furthermore, the link between splice acceptor choice and utilization of the nonconsensus splice donor is due to exon size, consistent with the exon recognition model of splicing.

乳头状瘤病毒引起鳞状上皮良性和恶性病变 高等脊椎动物的上皮细胞。 这些细胞的完整裂解周期 病毒（包括晚期基因表达）只发生在分化的 鳞状上皮细胞。 恶性病变和感染细胞 培养不产生病毒。 牛乳头瘤病毒1型（BPV-1）是 用作研究乳头瘤病毒晚期基因的模型系统 表达及其控制。 数据表明，晚期基因表达是 在多个转录和转录后水平调节。 BPV-1突变体以及真核表达载体已用于 表明BPV-1晚期多聚腺苷酸化位点可被有效利用， 即使在转化细胞中，晚期poly（A）位点也是一个更重要的位点。 有效的poly（A）位点比早期的poly（A）位点。 利用效率低下 晚期poly（A）位点在正常情况下的表达可能部分是由于 转录暂停之间的早期和晚期聚（A）的网站， 转化的细胞和部分到一个短的抑制元素在后期 3'UTR。 该晚期3' UTR元件通过以下方式显示不起作用： 使晚期mRNA不稳定，并可能在RNA加工或 运输水平。 也有证据表明BPV-1 poly（A）位点 选择可以由剪接因子调节。 目前的数据表明， 利用在nt 3225处的可变剪接受体， 在nt 3764处的弱非共有剪接供体的增强识别是 从早班到晚班的关键事件。 它显示，使用一个晚 由异源启动子驱动的小基因表达载体， nt 3225剪接受体突变，迫使使用nt 3605剪接 受体，突变的nt 3764剪接供体强共识 序列和营养复制都是必要的，也是足够的， 给出了RNA加工的晚期模式。 此外， 剪接受体的选择和非共有剪接供体的利用是 由于外显子大小，与剪接的外显子识别模型一致。