An mRNA m7G cap binding-like motif within human Ago2 represses translation
An mRNA m7G cap binding-like motif within human Ago2 represses translation
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DOI：
10.1016/j.cell.2007.05.016
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发表时间：
2007-06-15
期刊：
影响因子：
64.5
通讯作者：
Mourelatos, Zissimos
中科院分区：
文献类型：
--
作者：
Kiriakidou, Marianthi;Tan, Grace S.;Mourelatos, Zissimos
MicroRNAs(MiRNAs)与ArgAerte(AGO)蛋白结合，抑制翻译或促进mRNA靶标的降解。人let-7miRNA以m(7)G帽依赖的方式抑制mRNA靶的翻译起始，并似乎阻止蛋白质的产生，但涉及的分子机制(S)尚不清楚，AGO蛋白质在翻译调控中的作用仍不清楚。在这里，我们在AGO蛋白的中部结构域中发现了一个基序(MC)，它与必需的翻译起始因子elF4E的m(7)G帽结合结构域有很大的相似之处。我们在人Ago2的MC基序中发现了与m(7)G帽结合和翻译抑制所需的保守芳香族残基，但不影响Ago2与miRNA的组装或其催化活性。我们认为，Ago2通过与信使核糖核酸靶标的m(7)G帽结合来抑制信使核糖核酸翻译的启动，从而可能排除了elF4E的招募。
microRNAs (miRNAs) bind to Argonaute (Ago) proteins and inhibit translation or promote degradation of mRNA targets. Human let-7 miRNA inhibits translation initiation of mRNA targets in an m(7)G cap-dependent manner and also appears to block protein production, but the molecular mechanism(s) involved is unknown and the role of Ago proteins in translational regulation remains elusive. Here we identify a motif (MC) within the Mid domain of Ago proteins, which bears significant similarity to the m(7)G cap-binding domain of elF4E, an essential translation initiation factor. We identify conserved aromatic residues within the MC motif of human Ago2 that are required for binding to the m(7)G cap and for translational repression but do not affect the assembly of Ago2 with miRNA or its catalytic activity. We propose that Ago2 represses the initiation of mRNA translation by binding to the m(7)G cap of mRNA targets, thus likely precluding the recruitment of elF4E.