miRISC and the CCR4-NOT complex silence mRNA targets independently of 43S ribosomal scanning.
miRISC and the CCR4-NOT complex silence mRNA targets independently of 43S ribosomal scanning.
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DOI：
10.15252/embj.201592901
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发表时间：
2016-06-01
期刊：
影响因子：
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通讯作者：
Izaurralde E
中科院分区：
文献类型：
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作者：
Kuzuoğlu-Öztürk D;Bhandari D;Huntzinger E;Fauser M;Helms S;Izaurralde E
miRNA与Argonaute（AGO）蛋白结合，通过抑制翻译和促进去腺苷化、脱帽和mRNA降解来沉默mRNA靶点的表达。目前的沉默模型表明，AGO介导这些影响，通过连续招募的GW 182蛋白，CCR 4-NOT去腺苷酶复合物和翻译阻遏物和去帽激活DDX 6。另一种模型假定AGO通过在43 S核糖体扫描过程中干扰eIF 4A功能来抑制翻译，并且这种机制不依赖于GW 182和果蝇中的CCR 4-NOT复合物。在这里，我们发现miRNA，AGO，GW 182，CCR 4-NOT复合物和DDX 6/Me 31 B抑制和降解多聚腺苷酸化的mRNA靶点，这些靶点在人类和Dm细胞中通过非扫描依赖性机制翻译。这一和其他观察结果表明，这些蛋白质和miRNA介导沉默的共同机制。这种机制在核糖体扫描期间不需要eIF 4A功能。
miRNAs associate with Argonaute (AGO) proteins to silence the expression of mRNA targets by inhibiting translation and promoting deadenylation, decapping, and mRNA degradation. A current model for silencing suggests that AGOs mediate these effects through the sequential recruitment of GW182 proteins, the CCR4–NOT deadenylase complex and the translational repressor and decapping activator DDX6. An alternative model posits that AGOs repress translation by interfering with eIF4A function during 43S ribosomal scanning and that this mechanism is independent of GW182 and the CCR4–NOT complex in Drosophila melanogaster. Here, we show that miRNAs, AGOs, GW182, the CCR4–NOT complex, and DDX6/Me31B repress and degrade polyadenylated mRNA targets that are translated via scanning‐independent mechanisms in both human and Dm cells. This and additional observations indicate a common mechanism used by these proteins and miRNAs to mediate silencing. This mechanism does not require eIF4A function during ribosomal scanning.