Drosophila microRNAs are sorted into functionally distinct argonaute complexes after production by Dicer-1
Drosophila microRNAs are sorted into functionally distinct argonaute complexes after production by Dicer-1
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DOI：
10.1016/j.cell.2007.05.056
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发表时间：
2007-07-27
期刊：
影响因子：
64.5
通讯作者：
Zamore, Phillip D.
中科院分区：
文献类型：
--
作者：
Foerstemann, Klaus;Horwich, Michael D.;Zamore, Phillip D.
小干扰RNA（siRNA）和microRNA（miRNA）引导不同类型的RNA诱导沉默复合物（RISC）抑制从发育到抗病毒防御的生物过程中的mRNA表达。在果蝇中，不同但概念相似的核酸内切途径产生siRNA和miRNA。在这里，我们表明，尽管它们不同的生物起源，双链miRNA和siRNA参与一个共同的分选步骤，将它们分为Ago 1或Ago 2的效应复合物。这些不同的复合物通过不同的机制沉默它们的靶RNA。负载miRNA的Ago 2-RISC介导RNAi，但只有Ago 1能够抑制在其miRNA结合位点具有中心错配的mRNA。相反，Ago 1不能介导RNAi，因为它是一种低效的核酸酶，其催化速率受到其反应产物解离的限制。因此，Argonaute蛋白质的果蝇Ago亚进化枝的两个成员在功能上是特化的，但特定的小RNA类别并不限于与Ago 1或Ago 2相关联。
Small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide distinct classes of RNA-induced silencing complexes (RISCs) to repress mRNA expression in biological processes ranging from development to antiviral defense. In Drosophila, separate but conceptually similar endonucleolytic pathways produce siRNAs and miRNAs. Here, we show that despite their distinct biogenesis, double-stranded miRNAs and siRNAs participate in a common sorting step that partitions them into Ago1- or Ago2-containing effector complexes. These distinct complexes silence their target RNAs by different mechanisms. miRNA-loaded Ago2-RISC mediates RNAi, but only Ago1 is able to repress an mRNA with central mismatches in its miRNA-binding sites. Conversely, Ago1 cannot mediate RNAi, because it is an inefficient nuclease whose catalytic rate is limited by the dissociation of its reaction products. Thus, the two members of the Drosophila Ago subclade of Argonaute proteins are functionally specialized, but specific small RNA classes are not restricted to associate with Ago1 or Ago2.