Regulation of alternative splicing in Drosophila by 56 RNA binding proteins.
Regulation of alternative splicing in Drosophila by 56 RNA binding proteins.
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DOI：
10.1101/gr.192518.115
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发表时间：
2015-11
期刊：
影响因子：
7
通讯作者：
Brenner SE
中科院分区：
文献类型：
--
作者：
Brooks AN;Duff MO;May G;Yang L;Bolisetty M;Landolin J;Wan K;Sandler J;Booth BW;Celniker SE;Graveley BR;Brenner SE
选择性剪接是由RNA结合蛋白(RBPs)调控的，它识别前mRNA序列元件并激活或抑制相邻的外显子。在这里，我们使用RNA干扰和RNA-SEQ来识别由56个果蝇蛋白质调控的剪接事件，其中一些以前未知的蛋白质调控剪接。几乎所有的蛋白质都影响第一外显子的选择，表明限制性商业惯例在第一外显子的选择中起着重要作用。一半的剪接事件受到多个蛋白质的调控，表现出广泛的组合调控。我们观察到SR和hnRNP蛋白倾向于相互协调作用，而不是相互拮抗。我们还发现了一个跨调控网络，其中剪接调控因子影响了编码其他剪接调控因子的前mRNAs的剪接。这项大规模研究大大提高了我们对最近剪接调控模型的理解，并提供了由56种不同限制性商业惯例调控的数千个外显子的来源。
Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila proteins, some previously unknown to regulate splicing. Nearly all proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected the splicing of pre-mRNAs encoding other splicing regulators. This large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs.