Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6059, USA.
Trends Biochem Sci. 2011 Aug;36(8):397-404. doi: 10.1016/j.tibs.2011.04.003. Epub 2011 May 17.
With recent advances in microarrays and sequencing it is now relatively straightforward to compare pre-mRNA splicing patterns in different cellular conditions on a genome-wide scale. Such studies have revealed extensive changes in cellular splicing programs in response to stimuli such as neuronal depolarization, DNA damage, immune signaling and cellular metabolic changes. However, for many years our understanding of the signaling pathways responsible for such splicing changes was greatly lacking. Excitingly, over the past few years this gap has begun to close. Recent studies now suggest notable trends in the mechanisms that link cellular stimuli to downstream alternative splicing events. These include regulated synthesis or degradation of splicing factors, differential protein-protein interactions, altered nuclear translocation and changes in transcription elongation.
随着微阵列和测序技术的最新进展，现在相对容易在全基因组范围内比较不同细胞条件下的前体 mRNA 剪接模式。此类研究揭示了细胞剪接程序在响应神经元去极化、DNA 损伤、免疫信号和细胞代谢变化等刺激时发生的广泛变化。然而，多年来，我们对负责这些剪接变化的信号通路的理解非常缺乏。令人兴奋的是，在过去的几年中，这种差距开始缩小。最近的研究表明，将细胞刺激与下游选择性剪接事件联系起来的机制存在显著趋势。这些机制包括剪接因子的合成或降解的调节、差异蛋白-蛋白相互作用、核转位的改变以及转录延伸的变化。
