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 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.
Katsanou
Vicky
V
Institute of Immunology, Biomedical Sciences Research Center Alexander Fleming, 16672 Vari, Greece.
Papadaki
Olympia
O
Milatos
Stavros
S
Blackshear
Perry J
PJ
Anderson
Paul
P
Kollias
George
G
Kontoyiannis
Dimitris L
DL
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D000954:Antigens, Surface; D016207:Cytokines; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins