Positive and negative feedback loops in the p53 and mRNA 3' processing pathways

Emral Devany, Xiaokan Zhang, Ji Yeon Park, Bin Tian, Frida Esther Kleiman

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Although the p53 network has been intensively studied, genetic analyses long hinted at the existence of components that remained elusive. Recent studies have shown regulation of p53 at the mRNA level mediated via both the 5' and the 3' untranslated regions and affecting the stability and translation efficiency of the p53 mRNA. Here, we provide evidence of a feedback loop between p53 and the poly(A)-specific ribonuclease (PARN), in which PARN deadenylase keeps p53 levels low in nonstress conditions by destabilizing p53 mRNA, and the UV-induced increase in p53 activates PARN deadenylase, regulating gene expression during DNA damage response in a transactivation-independent manner. This model is innovative because it provides insights into p53 function and the mechanisms behind the regulation of mRNA 3' end processing in different cellular conditions.

Original languageEnglish (US)
Pages (from-to)3351-3356
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - Feb 26 2013

All Science Journal Classification (ASJC) codes

  • General


  • Deadenylation
  • Gene expression control
  • MRNA 3' processing
  • MRNA steady state levels


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