Rbm24, an RNA-binding Protein and a Target of p53, Regulates p21 Expression via mRNA Stability

Background: Post-transcriptional regulation of p21 expression is still not fully understood. Results: Rbm24 is induced by p53 and serves as a mediator of p53 to regulate p21 expression via binding to its 3-UTR. Conclusion: Rbm24, an RNA-binding protein and a target of p53, enhances p21 expression via mRNA stability. Significance: A novel p53 target gene Rbm24 is identified to regulate p21 mRNA stability. p21, a cyclin-dependent kinase inhibitor, is necessary for proper control of the cell cycle and premature senescence. Thus, p21 expression needs to be tightly controlled. In this study, we found that Rbm24, an RNA-binding protein and a target gene of the p53 protein, can regulate p21 expression via mRNA stability. Specifically, we showed that Rbm24 is induced by DNA damage and Mdm2 inhibitor Nutlin-3. We also found that p53 protein binds to and activates the promoter of the Rbm24 gene. Moreover, we found that overexpression of Rbm24 increases, whereas knockdown of Rbm24 decreases, p21 mRNA and protein expression. In addition, we demonstrated that overexpression of Rbm24 enhances the half-life of p21 transcript. Consistent with this, we provided evidence that Rbm24 binds to the 3-untranslated region (3-UTR) of p21 transcript and an AU/U-rich element in the p21 3-UTR is necessary for Rbm24 to increase p21 expression. Finally, we showed that the RNA recognition motif in Rbm24 is required for binding to p21 transcript and subsequently for inducing p21 expression. Altogether, we uncovered that Rbm24 is a novel player in the p53 pathway, which may be explored to restore proper cell cycle control in p53-deficient tumors via p21.