Banting and Best Department of Medical Research and Department of Molecular Genetics, Donnelly Centre, University of Toronto, 160 College Street, Room 1016, Toronto, ON M5S 3E1, Canada.
Biochem Cell Biol. 2012 Oct;90(5):603-12. doi: 10.1139/o2012-019. Epub 2012 Jul 11.
During the past ten years, remarkable progress has been made in our understanding of the complexity and regulation of alternative splicing. The generation of large datasets of quantitative alternative splicing profiling information has revealed that transcripts from at least 95% of multi-exon human genes undergo alternative splicing, and that thousands of exons in mammalian transcriptomes are subject to striking regulatory patterns. Together with advanced computational methods, these datasets have enabled the inference of a predictive code for tissue-dependent alternative splicing. This code has further provided new insight into splicing regulatory mechanisms. Collectively, these approaches are revealing the existence of discrete networks of exons that are coordinately regulated in diverse biologically normal and disease contexts. A major challenge ahead is to systematically determine the functions of exons comprising these exon networks as well as the factors and mechanisms responsible for their regulation. This perspective provides an account of progress in these areas and also discusses future avenues of exon-centric exploration.
在过去的十年中，我们对可变剪接的复杂性和调控的理解取得了显著的进展。大量的定量可变剪接谱分析数据集的产生揭示了至少 95%的多外显子人类基因的转录本都经历了可变剪接，而且哺乳动物转录组中的数千个外显子受到显著的调控模式的影响。这些数据集与先进的计算方法一起，使得可以推断出组织依赖性可变剪接的预测性编码。这个编码进一步为剪接调控机制提供了新的见解。总的来说，这些方法揭示了离散的外显子网络的存在，这些外显子网络在不同的生物正常和疾病环境中是协调调控的。未来的一个主要挑战是系统地确定这些外显子网络的外显子的功能，以及负责它们调控的因素和机制。这一观点提供了这些领域进展的说明，并讨论了以外显子为中心的探索的未来途径。
