剪接体
RNA剪接
转录组
计算生物学
芯(光纤)
生物
遗传学
基因
计算机科学
基因表达
核糖核酸
电信
作者
Malgorzata Ewa Rogalska,Estefanía Mancini,Sophie Bonnal,André Gohr,Bryan M. Dunyak,Niccolò Arecco,Peter G. Smith,Frédéric H. Vaillancourt,Juan Valcárcel
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2024-10-31
卷期号:386 (6721): 551-560
标识
DOI:10.1126/science.adn8105
摘要
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.
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