title: Rbm24, an RNA-binding protein and a target of p53, regulates p21 expression via mRNA stability.
abstract: 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.
authors.affiliation: From the Comparative Oncology Laboratory, University of California, Davis, California 95616.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Jiang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Yingjuan
authors.initials: Y
authors.lastname: Qian
authors.forename: Enshun
authors.initials: E
authors.lastname: Xu
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Xinbin
authors.initials: X
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology*; D020816:Amino Acid Motifs; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D020871:RNA Stability / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Cancer Biology; Cell Cycle; RNA-binding Protein; mRNA Decay; p53