Pleiss Jeffrey A, Whitworth Gregg B, Bergkessel Megan, Guthrie Christine
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, Genentech Hall, Room N-374, San Francisco, CA 94143-2200, USA.
Mol Cell. 2007 Sep 21;27(6):928-37. doi: 10.1016/j.molcel.2007.07.018.
While the core splicing machinery is highly conserved between budding yeast and mammals, the absence of alternative splicing in Saccharomyces cerevisiae raises the fundamental question of why introns have been retained in approximately 5% of the 6000 genes. Because ribosomal protein-encoding genes (RPGs) are highly overrepresented in the set of intron-containing genes, we tested the hypothesis that splicing of these transcripts would be regulated under conditions in which translation is impaired. Using a microarray-based strategy, we find that, within minutes after the induction of amino acid starvation, the splicing of the majority of RPGs is specifically inhibited. In response to an unrelated stress, exposure to toxic levels of ethanol, splicing of a different group of transcripts is inhibited, while the splicing of a third set is actually improved. We propose that regulation of splicing, like transcription, can afford rapid and specific changes in gene expression in response to the environment.
虽然在出芽酵母和哺乳动物之间核心剪接机制高度保守，但酿酒酵母中不存在可变剪接这一情况引发了一个基本问题：为何在6000个基因中约5%的基因保留了内含子。由于核糖体蛋白编码基因（RPG）在含内含子基因集中高度富集，我们检验了这样一个假设：在翻译受损的条件下，这些转录本的剪接会受到调控。使用基于微阵列的策略，我们发现，在诱导氨基酸饥饿后的几分钟内，大多数RPG的剪接会被特异性抑制。响应一种不相关的应激，即暴露于有毒水平的乙醇时，另一组转录本的剪接受到抑制，而第三组转录本的剪接实际上得到改善。我们提出，剪接的调控与转录一样，能够在响应环境时实现基因表达的快速且特异性变化。
