Posttranscriptional regulation of 14-3-3 by RNA-binding protein HuR modulating intestinal epithelial restitution after wounding

The 14-3-3 is a member of the family of 14-3-3 proteins and participates in many aspects of cellular processes, but its regulation and involvement in gut mucosal homeostasis remain unknown. Here, we report that 14-3-3 expression is tightly regulated at the posttranscription level by RNA-binding protein HuR and plays an important role in early intestinal epithelial restitution after wounding. The 14-3-3 was highly expressed in the mucosa of gastrointestinal tract and in cultured intestinal epithelial cells (IECs). The 3 untranslated region (UTR) of the 14-3-3 mRNA was bound to HuR, and this association enhanced 14-3-3 translation without effect on its mRNA content. Conditional target deletion of HuR in IECs decreased the level of 14-3-3 protein in the intestinal mucosa. Silencing 14-3-3 by transfection with specific siRNA targeting the 14-3-3 mRNA suppressed intestinal epithelial restitution as indicated by a decrease in IEC migration after wounding, whereas ectopic overexpression of the wild-type 14-3-3 promoted cell migration. These resultsindicate that HuR induces 14-3-3 translation via interaction with its 3 UTR and that 14-3-3 is necessary for stimulation of IEC migration after wounding.