Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties.
Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties.
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DOI：
10.1016/j.cell.2012.10.036
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发表时间：
2012-11-21
期刊：
影响因子：
64.5
通讯作者：
Zamore PD
中科院分区：
文献类型：
--
作者：
Wee LM;Flores-Jasso CF;Salomon WE;Zamore PD
MicroRNA（miRNAs）和小干扰RNA（siRNAs）引导Argonaute蛋白沉默mRNA表达。Argonaute结合改变了RNA向导的性质，产生了功能结构域。我们发现Argonaute建立的结构域--锚区、种子区、中心区、3′补充区和尾区--具有不同的生物化学特性，这些特性解释了动物miRNA和siRNA如何结合其靶点之间的差异。siRNA与其靶标之间的广泛互补性减缓了果蝇Argonaute 2（Ago 2）与靶标结合和解离的速率。强调其在抗病毒防御中的作用，苍蝇Ago 2从广泛互补的靶RNA中解离得如此缓慢，以至于基本上每个完全配对的靶都被切割。相反，小鼠AGO 2，主要介导miRNA介导的抑制，解离迅速，完全配对和种子匹配的目标具有相似的速率。我们的数据缩小了Argonaute结合的siRNA和miRNA如何找到，结合和调节其靶标的生物化学合理模型的范围。
MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) guide Argonaute proteins to silence mRNA expression. Argonaute binding alters the properties of an RNA guide, creating functional domains. We show that the domains established by Argonaute— the anchor, seed, central, 3′ supplementary, and tail regions—have distinct biochemical properties that explain the differences between how animal miRNAs and siRNAs bind their targets. Extensive complementarity between an siRNA and its target slows the rate at which fly Argonaute2 (Ago2) binds to and dissociates from the target. Highlighting its role in antiviral defense, fly Ago2 dissociates so slowly from extensively complementary target RNAs that essentially every fully paired target is cleaved. Conversely, mouse AGO2, which mainly mediates miRNA-directed repression, dissociates rapidly and with similar rates for fully paired and seed-matched targets. Our data narrow the range of biochemically reasonable models for how Argonaute-bound siRNAs and miRNAs find, bind, and regulate their targets.
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