The Down syndrome cell adhesion molecule (Dscam) gene has essential roles in neural wiring and pathogen recognition in Drosophila melanogaster. Dscam encodes 38,016 distinct isoforms via extensive alternative splicing. The 95 alternative exons in Dscam are organized into clusters that are spliced in a mutually exclusive manner. The exon 6 cluster contains 48 variable exons and uses a complex system of competing RNA structures to ensure that only one variable exon is included. Here we show that the heterogeneous nuclear ribonucleoprotein hrp36 acts specifically within, and throughout, the exon 6 cluster to prevent the inclusion of multiple exons. Moreover, hrp36 prevents serine/arginine-rich proteins from promoting the ectopic inclusion of multiple exon 6 variants. Thus, the fidelity of mutually exclusive splicing in the exon 6 cluster is governed by an intricate combination of alternative RNA structures and a globally acting splicing repressor.

中文翻译：

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Dscam互斥拼接保真度的调节器。

唐氏综合征细胞粘附分子 (Dscam) 基因在黑腹果蝇的神经布线和病原体识别中具有重要作用。Dscam 通过广泛的选择性剪接对 38,016 种不同的异构体进行编码。Dscam 中的 95 个替代外显子被组织成以互斥方式拼接的簇。外显子 6 簇包含 48 个可变外显子，并使用竞争性 RNA 结构的复杂系统来确保仅包含一个可变外显子。在这里，我们展示了异质核核糖核蛋白 hrp36 在外显子 6 簇内和整个过程中的作用，以防止包含多个外显子。此外，hrp36 可防止富含丝氨酸/精氨酸的蛋白质促进多个外显子 6 变体的异位包含。因此，