Kelly J J, Wildeman A G
Department of Molecular Biology and Genetics, University of Guelph, Ontario, Canada.
Nucleic Acids Res. 1991 Dec 25;19(24):6799-804. doi: 10.1093/nar/19.24.6799.
Simian virus 40 large tumor antigen is a multifunctional protein, with two of its roles being the promotion of viral DNA replication and replication-independent activation of viral transcription. Replication leads to a shift in transcription from the early-early to the late and late-early cap sites, through mechanisms poorly understood. The viral transcription enhancer contains sequences important for both early and late transcription, and we therefore have carried out experiments to evaluate its role in these events. We find that the ability of replication to lead to a shift diminishes when early-early transcription is made increasingly stronger by multimerizing the enhancer, and suggest that replication might lead to the shift by interfering with the ability of the enhancer to direct initiation to those sites. The natural situation in the virus of having two copies of this element might represent a compromise between maximizing both T antigen expression early in infection and late gene expression after replication begins. We also show that replication-independent transcription activation by T antigen is bidirectional and involves at least in part elements to which the factor TEF-1 binds.
猴病毒40大T抗原是一种多功能蛋白，其作用之一是促进病毒DNA复制，另一个作用是在不依赖复制的情况下激活病毒转录。通过尚不清楚的机制，复制会导致转录从早期-早期帽位点转变为晚期和晚期-早期帽位点。病毒转录增强子包含对早期和晚期转录都很重要的序列，因此我们进行了实验来评估其在这些事件中的作用。我们发现，通过使增强子多聚化来增强早期-早期转录时，复制导致转录转变的能力减弱，这表明复制可能通过干扰增强子将起始转录引导至那些位点的能力来导致转录转变。病毒中该元件有两个拷贝的自然情况可能代表了在感染早期最大化T抗原表达与复制开始后晚期基因表达之间的一种折衷。我们还表明，T抗原不依赖复制的转录激活是双向的，并且至少部分涉及因子TEF-1结合的元件。
