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PMID:16168373

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Citation

Katsanou, V, Papadaki, O, Milatos, S, Blackshear, PJ, Anderson, P, Kollias, G and Kontoyiannis, DL (2005) HuR as a negative posttranscriptional modulator in inflammation. Mol. Cell 19:777-89

Abstract

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.

Links

PubMed Online version:10.1016/j.molcel.2005.08.007

Keywords

Animals; Antigens, Surface/genetics; Antigens, Surface/metabolism; Cells, Cultured; Cytokines/genetics; Cytokines/immunology; 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

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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