The RNA helicase Aquarius exhibits structural adaptations mediating its recruitment to spliceosomes
The RNA helicase Aquarius exhibits structural adaptations mediating its recruitment to spliceosomes
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DOI：
10.1038/nsmb.2951
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发表时间：
2015-02-01
影响因子：
16.8
通讯作者：
Pena, Vladimir
中科院分区：
文献类型：
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作者：
De, Inessa;Sessonov, Sergey;Pena, Vladimir
水瓶座是一种多功能的RNA解旋酶，它在特定的位置结合前体-mRNA内含子。在这里，我们报告了人类水瓶座的晶体结构，揭示了一个中心RNA解旋酶核心和几个独特的附属结构域，包括一个手臂重复结构域。我们发现水瓶座作为五聚体内含子结合复合体(IBC)的一部分整合到剪接体中，该复合体与臂结构域一起与激活的剪接体中的U2 SnRNP蛋白交联；这表明后者有助于水瓶座在内含子上的定位。水瓶座的手臂结构域对于IBC的形成是必不可少的，因此表明它具有关键的蛋白质-蛋白质支架作用。最后，我们提供了水瓶座在体外进行有效的前体-mRNA剪接所必需的证据。我们的发现突出了解旋酶的显着结构适应性，以实现位置特异性募集到核糖核蛋白复合体，并揭示了人类剪接体的新构件。
Aquarius is a multifunctional putative RNA helicase that binds precursor-mRNA introns at a defined position. Here we report the crystal structure of human Aquarius, revealing a central RNA helicase core and several unique accessory domains, including an ARM-repeat domain. We show that Aquarius is integrated into spliceosomes as part of a pentameric intron-binding complex (IBC) that, together with the ARM domain, cross-links to U2 snRNP proteins within activated spliceosomes; this suggests that the latter aid in positioning Aquarius on the intron. Aquarius's ARM domain is essential for IBC formation, thus indicating that it has a key protein-protein scaffolding role. Finally, we provide evidence that Aquarius is required for efficient precursor-mRNA splicing in vitro. Our findings highlight the remarkable structural adaptations of a helicase to achieve position-specific recruitment to a ribonucleoprotein complex and reveal a new building block of the human spliceosome.