MicroRNAs (miRNAs) recruit the RNA-induced silencing complex (RISC) to repress the translation of target mRNAs. While the 5′ 7-methylguanosine cap of target mRNAs has been well known to be important for miRNA repression, the underlying mechanism is not clear. Here we show that TNRC6A interacts with eIF4E2, a homologue of eIF4E that can bind to the cap but cannot interact with eIF4G to initiate translation, to inhibit the translation of target mRNAs. Downregulation of eIF4E2 relieved miRNA repression of reporter expression. Moreover, eIF4E2 downregulation increased the protein levels of endogenous IMP1, PTEN and PDCD4, whose expression are repressed by endogenous miRNAs. We further provide evidence showing that miRNA enhances eIF4E2 association with the target mRNA. We propose that miRNAs recruit eIF4E2 to compete with eIF4E to repress mRNA translation.

中文翻译：

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MicroRNAs 招募 eIF4E2 来抑制目标 mRNA 的翻译

MicroRNA (miRNA) 招募 RNA 诱导的沉默复合物 (RISC) 来抑制目标 mRNA 的翻译。虽然众所周知靶 mRNA 的 5' 7-甲基鸟苷帽对于 miRNA 抑制很重要，但其潜在机制尚不清楚。在这里，我们展示了 TNRC6A 与 eIF4E2 相互作用，eIF4E2 是 eIF4E 的同系物，可以与帽结合但不能与 eIF4G 相互作用以启动翻译，以抑制目标 mRNA 的翻译。eIF4E2 的下调解除了 miRNA 对报告基因表达的抑制。此外，eIF4E2 下调增加了内源性 IMP1、PTEN 和 PDCD4 的蛋白质水平，其表达受到内源性 miRNA 的抑制。我们进一步提供证据表明 miRNA 增强了 eIF4E2 与目标 mRNA 的关联。