CONTROL OF PAPILLOMAVIRUS LATE TRANSCRIPTION

乳头瘤病毒可引起鳞状细胞癌的良性和恶性病变 高等脊椎动物的上皮细胞。它们的完整的裂解循环 病毒(包括晚期基因表达)仅发生在分化的 鳞状上皮细胞。恶性病变和感染细胞 培养物不会产生病毒。牛乳头瘤病毒1型(BPV-1) 作为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上进行调控。 BPV-1突变体和真核表达载体已被用于 表明BPV-1晚期多聚腺苷基化位点可以被有效利用， 即使在转化的细胞中，晚期的聚(A)位点是更多的 有效的多聚(A)位点比早期的多聚(A)位点。低效利用 在正常情况下的晚期聚(A)位点的部分原因可能是 早期和晚期Poly(A)位点之间的转录暂停 转化细胞，并在后期部分转化为短抑制元件 3‘非编码区。该晚期3‘非编码区元件通过以下方式显示不起作用 破坏晚期mRNA的稳定，并可能在RNA加工或 运输层。也有证据表明BPV-1聚(A)位点 选择可能受到剪接因子的调节。目前的数据表明， NT 3225上的选择性剪接受体的利用 增强识别新台币3764位的弱非一致剪接供体 从早到晚的关键事件。它被展示出来，使用了一个很晚的 由异源启动子驱动的微型基因表达载体， NT 3225剪接受体突变，迫使使用NT 3605剪接 受体、突变的NT3764剪接供体达成强烈共识 序列和营养复制既是必要的也是充分的 给出一个RNA加工的晚期模式。此外，两者之间的联系 剪接受体的选择和非共识剪接供体的利用 由于外显子大小不同，符合外显子剪接识别模型。

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.