Long-range RNA pairings contribute to mutually exclusive splicing.
Long-range RNA pairings contribute to mutually exclusive splicing.
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长程 RNA 配对有助于互斥剪接
DOI：
10.1261/rna.053314.115
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Yue Y;Yang Y;Dai L;Cao G;Chen R;Hong W;Liu B;Shi Y;Meng Y;Shi F;Xiao M;Jin Y
互斥剪接是增加蛋白质库的重要手段，唐氏综合征细胞粘附分子（Dscam）基因可能在果蝇中产生38，016种不同的异构体。然而，由于Dscam外显子簇的复杂性，其调控机制仍然不清楚。在这里，我们揭示了一个分子模型的相互排斥剪接的蛇前mRNA的基础上上游和下游RNA配对之间的竞争的调节。这样的双RNA配对赋予包含替代外显子的微调。此外，我们还证明了选择性外显子的剪接结果是以相对配对强度相关模式介导的。结合比较基因组学分析和实验证据显示，在Dscam基因的外显子簇4和9中具有相似的双向结构架构。我们的研究结果提供了一个新的机制框架的相互排斥剪接的调节，并可能提供潜在的适用于在基因调控网络的远程RNA-RNA相互作用的见解。
Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA–RNA interactions in gene regulatory networks.