FUS is one of the causative factors of amyotrophic lateral sclerosis. Loss and/or gain of its physiological functions has been believed to be linked to the pathogenesis of this condition. However, its functions remain incompletely understood. This study dissected the domains of FUS regulating the expression of SnRNP70, which functions in mRNA splicing. Biochemical analysis revealed that all FUS domains except for RGG1 contribute to determining Snrnp70 transcript abundance and thus its protein abundance. RNA‐Seq analysis using the Gly‐rich domain‐deleted mutant coupled with snRNP70 knockdown revealed that FUS has a potential to regulate gene expression in both snRNP70‐dependent and snRNP70‐independent manners through the Gly‐rich domain. These results provide insight into molecular details of the regulation of gene expression by FUS.

中文翻译：

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剖析参与调节 SnRNP70 基因表达的 FUS 结构域

FUS 是肌萎缩侧索硬化的致病因素之一。其生理功能的丧失和/或获得被认为与这种疾病的发病机制有关。然而，它的功能仍然不完全了解。本研究剖析了 FUS 调节 SnRNP70 表达的结构域，SnRNP70 在 mRNA 剪接中起作用。生化分析表明，除 RGG1 之外的所有 FUS 结构域都有助于确定 Snrnp70 转录本丰度，从而确定其蛋白质丰度。使用富含 Gly 结构域删除的突变体结合 snRNP70 敲低的 RNA-Seq 分析表明，FUS 具有通过富含 Gly 结构域以 snRNP70 依赖性和 snRNP70 非依赖性方式调节基因表达的潜力。这些结果提供了对 FUS 基因表达调控的分子细节的深入了解。