Abstract
Activation of p53-dependent apoptosis is critical for tumor suppression but aberrant activation of p53 also leads to developmental defects and heart failure. Here, we found that Rbm24 RNA-binding protein, a target of p53, regulates p53 mRNA translation. Mechanistically, we found that through binding to p53 mRNA and interaction with translation initiation factor eIF4E, Rbm24 prevents eIF4E from binding to p53 mRNA and inhibits the assembly of translation initiation complex. Importantly, we showed that mice deficient in Rbm24 die in utero due to the endocardial cushion defect in the heart at least in part due to aberrant activation of p53-dependent apoptosis. We also showed that the heart developmental defect in Rbm24-null mice can be partially rescued by p53 deficiency through decreased apoptosis in the heart. Together, we postulate that the p53-Rbm24 loop is critical for the heart development and may be explored for mitigating congenital heart diseases and heart failure.
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Acknowledgments
This work is supported in part by NIH grants CA076069.
Authors’ contribution
Zhang M., Zhang Y., Xu E., Mohibi S., Jiang Y., de Anda D.M., and Zhang J. did the experiments; Zhang M., Zhang Y., Zhang J., and Chen X. analyzed the data and wrote the manuscript. All authors read and approved the manuscript.
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Zhang, M., Zhang, Y., Xu, E. et al. Rbm24, a target of p53, is necessary for proper expression of p53 and heart development. Cell Death Differ 25, 1118–1130 (2018). https://doi.org/10.1038/s41418-017-0029-8
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DOI: https://doi.org/10.1038/s41418-017-0029-8
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