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The tumor suppressor protein p53 plays a crucial role in mediating cell cycle arrest and apoptosis in response to cellular stress.p53 expression is regulated at multiple molecular levels and disruption of these regulatory mechanisms leads to altered expression of p53 and tumorigenesis.Recent studies have demonstrated critical post-transcriptional regulation of p53, mediated via both the 5 and 3 untranslated regions (UTRs) and affecting the translation of p53 mRNA.Both proteins and microRNAs (miRNAs) have been implicated in such regulation.A specific miRNA (miR-125b) binds to the p53 3UTR and inhibits translation whereas the RNA-binding protein HuR binds to AU-rich elements in the p53 3UTR in response to genotoxic stress and enhance protein expression.Interestingly, the binding site ofmiR-125b on the p53 3UTR is adjacent to the binding site of the HuR protein.The proximity of the binding sites for both miR125b and HuR suggests a crosstalk between the two in regulating p53 expression.We show that p53 protein levels increase after exposure to DNA-damaging UV radiation, and reach a maximum at four to six hours post exposure.A similar pattern of increase in HuR expression on UV exposure indicates a correlation between increased HuR expression andp53 mRNA translation.RNA-immunoprecipitation shows maximum binding of HuR to p53 mRNA at four hours after UV-exposure, corresponding to the highest level of p53 translation.Finally, we show the downregulation of p53 translation in MCF7 cells by overexpressing miR-125b, which can be rescued by HuR protein overexpression in the cells.This demonstrates an interplay between miR-125b and HuR interactions with the p53 mRNA, an effect that is recapitulated in UV-exposed cells.Together, these observations show an antagonistic effect between miR-125b and HuR binding to the p53 3UTR, leading to a coordinated and fine-tuned expression of p53 in response to genotoxic stress.