MicroRNAs recruit eIF4E2 to repress translation of target mRNAs

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-017-0444-0) contains supplementary material, which is available to authorized users.