HuR as a negative posttranscriptional modulator in inflammation
HuR as a negative posttranscriptional modulator in inflammation
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DOI：
10.1016/j.molcel.2005.08.007
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发表时间：
2005-09-16
期刊：
影响因子：
16
通讯作者：
Kontoyiannis, DL
中科院分区：
文献类型：
--
作者：
Katsanou, V;Papadaki, O;Kontoyiannis, DL
HuR是一种RNA结合蛋白，据称在携带富au元素（AREs）的炎症mrna的转录后激活中起作用。在这里，我们表明，诱导增加HuR在小鼠先天室抑制炎症反应在体内。在巨噬细胞中，HuR过表达诱导了特定细胞因子mrna的翻译沉默，尽管对其相应的营业额有积极或名义上的影响。通过使用ARE功能障碍的模型系统，我们证明在缺乏tristetrprolin的不稳定功能的情况下，HuR不会改变目标mrna的积累，而是与翻译沉默者TIA-1协同减少细胞因子mrna的翻译。我们的数据表明，通过与特定mRNA亚群和负转录后模块的功能相互作用，HuR在炎症中以多效性方式起作用。
HuR is an RNA binding protein with an alleged role in the posttranscriptional activation of inflammatory mRNAs bearing AU-rich elements (AREs). Here, we show that the inducible increase of HuR in murine innate compartments suppresses inflammatory responses in vivo. In macrophages, HuR overexpression induced the translational silencing of specific cytokine mRNAs despite positive or nominal effects on their corresponding turnover. By using a model system of ARE dysfunction, we demonstrate that HuR does not alter the accumulation of target mRNAs in the absence of the destabilizing functions of Tristetraprolin but synergizes with the translational silencer TIA-1 to reduce the translation of cytokine mRNAs. Our data suggest that HuR acts in a pleiotropic fashion in inflammation through its functional interactions with specific mRNA subsets and negative posttranscriptional modules.