Nordqvist K, Akusjärvi G
Department of Microbial Genetics, Karolinska Institutet, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1990 Dec;87(24):9543-7. doi: 10.1073/pnas.87.24.9543.
The adenovirus major late transcription unit accounts for most virus-specific transcription late after infection. All mRNAs expressed from this unit carry a short spliced leader, the so-called tripartite leader, attached to their 5' ends. Here we describe a function for an adenovirus gene product in the control of major late mRNA abundance. We show that early region 4 (E4) stimulates mRNA accumulation from tripartite leader intron-containing transcription units approximately 10-fold in short-term transfection assays. The effect was already detectable in nuclear RNA and was not due to a transcriptional activation through any of the major late promoter elements or through an effect at nuclear to cytoplasmic mRNA transport. A surprising positional effect of the intron was noted. To be E4 responsive, the intron had to be placed close to the pre-mRNA 5' end. The same intron located far downstream in the 3' untranslated region of the mRNA was not E4 responsive. The E4 enhancement was not dependent on specific virus exon or intron sequences. These results suggest that E4 modulates a general pathway in mammalian mRNA formation.
腺病毒主要晚期转录单位负责感染后期大多数病毒特异性转录。从该单位表达的所有mRNA在其5'端都带有一个短的剪接前导序列，即所谓的三联前导序列。在此，我们描述了腺病毒基因产物在控制主要晚期mRNA丰度中的一种功能。我们表明，在短期转染实验中，早期区域4（E4）可刺激含三联前导序列内含子的转录单位的mRNA积累约10倍。这种效应在核RNA中已可检测到，并且不是由于通过任何主要晚期启动子元件的转录激活或通过对核到细胞质mRNA转运的影响所致。注意到内含子有一个令人惊讶的位置效应。要对E4作出反应，内含子必须靠近前体mRNA的5'端。位于mRNA 3'非翻译区下游很远位置的相同内含子对E4无反应。E4的增强不依赖于特定的病毒外显子或内含子序列。这些结果表明，E4调节哺乳动物mRNA形成中的一条通用途径。
