Drosophila Argonaute1 and Argonaute2 Employ Distinct Mechanisms for Translational Repression
Drosophila Argonaute1 and Argonaute2 Employ Distinct Mechanisms for Translational Repression
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DOI：
10.1016/j.molcel.2009.02.010
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发表时间：
2009-04-10
期刊：
影响因子：
16
通讯作者：
Tomari, Yukihide
中科院分区：
文献类型：
--
作者：
Iwasaki, Shintaro;Kawamata, Tomoko;Tomari, Yukihide
microRNAs通过结合其靶mrna上的部分互补位点诱导翻译抑制。我们已经建立了一个体外系统，概括了两个果蝇Argonaute （Ago）亚家族蛋白Ago1和Ago2介导的翻译抑制。我们发现Ago1-RISC （rna诱导沉默复合体）主要通过atp依赖性缩短其mRNA靶标的聚(A)尾部来抑制翻译。Ago1-RISC还可以在帽识别后二次阻塞一个步骤。相比之下，Ago2-RISC竞争性地阻断elF4E与elF4G的相互作用，抑制cap功能。我们发现果蝇中的两种Ago蛋白通过不同的机制调节翻译，这可能会调和之前关于miRNAs如何抑制蛋白质合成的矛盾解释。
microRNAs induce translational repression by binding to partially complementary sites on their target mRNAs. We have established an in vitro system that recapitulates translational repression mediated by the two Drosophila Argonaute (Ago) subfamily proteins, Ago1 and Ago2. We find that Ago1-RISC (RNA-induced silencing complex) represses translation primarily by ATP-dependent shortening of the poly(A) tail of its mRNA targets. Ago1-RISC can also secondarily block a step after cap recognition. In contrast, Ago2-RISC competitively blocks the interaction of elF4E with elF4G and inhibits the cap function. Our finding that the two Ago proteins in flies regulate translation by different mechanisms may reconcile previous, contradictory explanations for how miRNAs repress protein synthesis.