Adami G, Babiss L E
Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021.
EMBO J. 1991 Nov;10(11):3457-65. doi: 10.1002/j.1460-2075.1991.tb04910.x.
Many cellular and viral genes are parts of complex transcription units containing multiple splicing choices. During the course of an adenoviral replicative cycle, different spliced versions of a single gene predominate, depending on the stage of infection. This is true for several adenoviral genes. In this paper we show for the viral E1B transcription unit that splice site usage regulates this process. The change in alternative splicing in this system does not depend on the sequence of the transcribed genes. Non-adenoviral genes, such as the SV40 early region and the polyoma early region, which normally show little or no regulation of spliced RNA product formation, become regulated for mRNA production after insertion into the adenoviral genome. Additional studies show that E1B splicing regulation in adenovirus is a cis effect. Staggered infections using two discernable viral genomes resulted in a situation where both early and late genomes exist in the same nucleus. Neither genome was able to impose its regulated splicing pattern on the other, indicating that the cue for the switch in viral gene splicing is not directly dependent on global changes in trans-acting splicing factors. This suggests a model where the signal for changes in RNA processing for the E1B gene is linked to the state of the DNA template or its localization within nuclear subcompartments.
许多细胞基因和病毒基因都是包含多种剪接选择的复杂转录单位的组成部分。在腺病毒复制周期中,单个基因的不同剪接版本占主导地位,这取决于感染阶段。几个腺病毒基因都是如此。在本文中,我们展示了对于病毒E1B转录单位,剪接位点的使用调控了这一过程。该系统中可变剪接的变化并不取决于转录基因的序列。非腺病毒基因,如SV40早期区域和多瘤病毒早期区域,通常对剪接RNA产物的形成几乎没有调控,但在插入腺病毒基因组后,其mRNA的产生受到了调控。进一步的研究表明,腺病毒中E1B的剪接调控是一种顺式效应。使用两种可区分的病毒基因组进行交错感染,导致早期和晚期基因组同时存在于同一个细胞核中。两种基因组都无法将其调控的剪接模式强加给另一种基因组,这表明病毒基因剪接切换的线索并不直接依赖于反式作用剪接因子的全局变化。这提示了一种模型,即E1B基因RNA加工变化的信号与DNA模板的状态或其在核亚区室中的定位有关。