Positive and negative feedback loops in the p53 and mRNA 3′ processing pathways
Positive and negative feedback loops in the p53 and mRNA 3′ processing pathways
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DOI：
10.1073/pnas.1212533110
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发表时间：
2013-02-26
影响因子：
11.1
通讯作者：
Kleiman, Frida Esther
中科院分区：
文献类型：
--
作者：
Devany, Emral;Zhang, Xiaokan;Kleiman, Frida Esther
尽管 p53 网络已被深入研究，但遗传分析长期以来一直暗示着仍然难以捉摸的成分的存在。最近的研究表明，p53 在 mRNA 水平上的调节是通过 5' 和 3' 非翻译区介导的，并影响 p53 mRNA 的稳定性和翻译效率。在这里，我们提供了 p53 和多聚腺苷酸特异性核糖核酸酶 (PARN) 之间反馈循环的证据，其中 PARN 去腺苷酶通过破坏 p53 mRNA 的稳定性，在非应激条件下保持 p53 水平较低，而紫外线诱导的 p53 增加激活 PARN 去腺苷酶，以不依赖反式激活的方式调节 DNA 损伤反应期间的基因表达。该模型具有创新性，因为它提供了对 p53 功能以及不同细胞条件下 mRNA 3' 末端加工调节背后机制的深入了解。
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.