研究人员报告了对305个剪接体组成成分和调节因子进行系统性敲低的人类癌细胞的转录组范围分析，以及重建管理不同类选择性剪接决策的功能剪接因子网络。结果揭示了剪接因子交叉调节的复杂回路，表明晚期组装的U4/U6.U5三小核糖核蛋白（snRNP）复合物的精确结构调节剪接位点配对，并发现U1 snRNP的蛋白成分在调节外显子定义和选择性5′剪接位点选择中的前所未有的分工。因此，研究人员提供了一个资源，以探索剪接调节的生理和病理机制。
据悉，剪接体是复杂的分子机械，在真核生物的信使RNA前体上依次组装以去除内含子（前mRNA剪接），这一生理调节过程在多种病理中发生变化。
附：英文原文
Title: Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome
Author: Malgorzata E. Rogalska, Estefania Mancini, Sophie Bonnal, André Gohr, Bryan M. Dunyak, Niccolò Arecco, Peter G. Smith, Frédéric H. Vaillancourt, Juan Valcárcel
Issue&Volume: 2024-11-01
Abstract: The spliceosome is the complex molecular machinery that sequentially assembles on eukaryotic messenger RNA precursors to remove introns (pre-mRNA splicing), a physiologically regulated process altered in numerous pathologies. We report transcriptome-wide analyses upon systematic knock down of 305 spliceosome components and regulators in human cancer cells and the reconstruction of functional splicing factor networks that govern different classes of alternative splicing decisions. The results disentangle intricate circuits of splicing factor cross-regulation, reveal that the precise architecture of late-assembling U4/U6.U5 tri–small nuclear ribonucleoprotein (snRNP) complexes regulates splice site pairing, and discover an unprecedented division of labor among protein components of U1 snRNP for regulating exon definition and alternative 5′ splice site selection. Thus, we provide a resource to explore physiological and pathological mechanisms of splicing regulation.
DOI: adn8105
Source: https://www.science.org/doi/10.1126/science.adn8105