HuR as a Negative Posttranscriptional Modulator in Inflammation

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...

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Bibliographic Details
Published in:Molecular cell 2005-09, Vol.19 (6), p.777-789
Main Authors: Katsanou, Vicky, Papadaki, Olympia, Milatos, Stavros, Blackshear, Perry J., Anderson, Paul, Kollias, George, Kontoyiannis, Dimitris L.
Format: Article
Language:English
Subjects:
Animals
Antigens, Surface - genetics
Antigens, Surface - metabolism
Cells, Cultured
Cytokines - genetics
Cytokines - immunology
ELAV Proteins
ELAV-Like Protein 1
Gene Expression Regulation
Humans
Inflammation
Liver - cytology
Liver - immunology
Macrophages - cytology
Macrophages - immunology
Mice
Mice, Transgenic
Protein Biosynthesis
RNA Stability
RNA, Messenger - metabolism
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
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Summary: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.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2005.08.007