HuR as a negative posttranscriptional modulator in inflammation

被引:211
作者
Katsanou, V
Papadaki, O
Milatos, S
Blackshear, PJ
Anderson, P
Kollias, G
Kontoyiannis, DL [1 ]
机构
[1] Biomed Sci Res Ctr Alexander Fleming, Inst Immunol, Vari 16672, Greece
[2] Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA
[3] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA
关键词
D O I
10.1016/j.molcel.2005.08.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:777 / 789
页数:13
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