TY - JOUR
T1 - Positive and negative feedback loops in the p53 and mRNA 3' processing pathways
AU - Devany, Emral
AU - Zhang, Xiaokan
AU - Park, Ji Yeon
AU - Tian, Bin
AU - Kleiman, Frida Esther
PY - 2013/2/26
Y1 - 2013/2/26
N2 - 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.
AB - 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.
KW - Deadenylation
KW - Gene expression control
KW - MRNA 3' processing
KW - MRNA steady state levels
UR - http://www.scopus.com/inward/record.url?scp=84874453925&partnerID=8YFLogxK
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U2 - 10.1073/pnas.1212533110
DO - 10.1073/pnas.1212533110
M3 - Article
C2 - 23401530
AN - SCOPUS:84874453925
SN - 0027-8424
VL - 110
SP - 3351
EP - 3356
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 9
ER -