Rbm24, a target of p53, is necessary for proper expression of p53 and heart development

Min Zhang, Yanhong Zhang, Enshun Xu, Shakur Mohibi, Danielle Michelle de Anda, Yuqian Jiang, Jin Zhang, Xinbin Chen

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalCell Death and Differentiation
DOIs
StateAccepted/In press - Jan 22 2018

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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