The Francis Crick Institute, London NW1 1AT, UK; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 3E1, Canada.
Mol Cell. 2019 Oct 17;76(2):329-345. doi: 10.1016/j.molcel.2019.09.017.
High-throughput sequencing-based methods and their applications in the study of transcriptomes have revolutionized our understanding of alternative splicing. Networks of functionally coordinated and biologically important alternative splicing events continue to be discovered in an ever-increasing diversity of cell types in the context of physiologically normal and disease states. These studies have been complemented by efforts directed at defining sequence codes governing splicing and their cognate trans-acting factors, which have illuminated important combinatorial principles of regulation. Additional studies have revealed critical roles of position-dependent, multivalent protein-RNA interactions that direct splicing outcomes. Investigations of evolutionary changes in RNA binding proteins, splice variants, and associated cis elements have further shed light on the emergence, mechanisms, and functions of splicing networks. Progress in these areas has emphasized the need for a coordinated, community-based effort to systematically address the functions of individual splice variants associated with normal and disease biology.
基于高通量测序的方法及其在转录组研究中的应用，彻底改变了我们对可变剪接的认识。在生理正常和疾病状态下，越来越多的细胞类型中，不断发现具有功能协调和生物学重要性的可变剪接事件的网络。这些研究还辅以努力定义控制剪接的序列代码及其同源反式作用因子，这揭示了调控的重要组合原则。进一步的研究揭示了位置依赖的、多价的蛋白质-RNA 相互作用在指导剪接结果方面的关键作用。对 RNA 结合蛋白、剪接变体和相关顺式元件进化变化的研究进一步阐明了剪接网络的出现、机制和功能。这些领域的进展强调了需要协调一致的、基于社区的努力，系统地解决与正常和疾病生物学相关的单个剪接变体的功能。
