Neel H, Weil D, Giansante C, Dautry F
Laboratoire d'Oncologie Moléculaire, Centre National de la Recherche Scientifique (CNRS) UA 1158, Institut Gustave Roussy, Villejuif, France.
Genes Dev. 1993 Nov;7(11):2194-205. doi: 10.1101/gad.7.11.2194.
In higher eukaryotes the large number of introns present in most genes implies that the pre-mRNA processing machinery should be efficient and accurate. Although this could be achieved at the level of each intron, an attractive alternative would be that interactions between introns improve the performance of this machinery. In this study we tested this hypothesis by comparing the processing of transcripts of the tumor necrosis factor beta gene, which differ only by their number of introns. We took advantage of the ordered splicing of the three introns present in this gene to design constructs that should generate, as primary transcripts, molecules that are normally produced by splicing. We established that the apparent splicing rate of intron 3 is increased 2.5- and 3.5-fold by the presence of one or two other introns on the primary transcript, respectively. Similarly, the apparent splicing rate of intron 2 is increased by the presence of intron 1. As these effects involve the splice sites of the upstream intron, these observations support the existence of cooperative interactions between introns during pre-mRNA processing.
在高等真核生物中，大多数基因中存在大量内含子，这意味着前体mRNA加工机制应该高效且准确。虽然这可以在每个内含子水平上实现，但一个有吸引力的替代方案是内含子之间的相互作用可提高该机制的性能。在本研究中，我们通过比较肿瘤坏死因子β基因转录本的加工过程来检验这一假设，这些转录本仅在其内含子数量上有所不同。我们利用该基因中存在的三个内含子的有序剪接来设计构建体，这些构建体作为初级转录本应产生通常通过剪接产生的分子。我们确定，初级转录本上存在一个或两个其他内含子时，内含子3的表观剪接速率分别提高了2.5倍和3.5倍。同样，内含子1的存在会提高内含子2的表观剪接速率。由于这些效应涉及上游内含子的剪接位点，这些观察结果支持在前体mRNA加工过程中内含子之间存在协同相互作用。
