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miR-21, an oncogenic miRNA, inhibits the translation of the pro-inflammatory tumor suppressor gene programmed cell death 4 (PDCD4) by binding to a target site within the 3’UTR of PDCD4 mRNA. By RNA affinity chromatography and identification of the binding proteins by mass spectrometry, we have found Annexin A2 (ANXA2) as a novel RNA-binding protein that associates with the PDCD4 mRNA. Increased level of ANXA2 in MCF7 cells correlates with decreased level of PDCD4 protein and the effect is mediated through the 3’UTR of the PDCD4 mRNA. ANXA2 binds to the PDCD4 mRNA 3’UTR, preferentially to a site towards the 3’ end of the mRNA. UV irradiation causes induction of ANXA2 protein which correlates with decreased PDCD4 protein and also decreased PDCD4 mRNA association with polysomes, suggesting translational repression. PDCD4 mRNA appears to associate with heavy cytoplasmic granules which might contain ANXA2 protein, thereby trapping PDCD4 mRNA in cytoplasmic foci. UV irradiation also induces miR-21 levels in MCF7 cells. ANXA2 knockdown prevents the induction of miR-21 post UV irradiation. This suggests a dual regulatory role of ANXA2 in translation repression of PDCD4 by direct binding to the mRNA and by indirectly inducing the binding of miR-21. |