Early exposure to IL-4 stabilizes IL-4 mRNA in CD4+ T cells via RNA-binding protein HuR.
The mechanisms regulating IL-4 mRNA stability in differentiated T cells are not known. We found that early exposure of CD4+ T cells to endogenous IL-4 increased IL-4 mRNA stability. This effect of IL-4 was mediated by the RNA-binding protein HuR. IL-4 mRNA interacted with HuR and the dominant binding site was shown within the coding region of IL-4 mRNA. Exposure of CD4+ T cells to IL-4 had no effects on HuR expression or subcellular localization, but triggered HuR binding to IL-4 mRNA. Thus, IL-4 plays a positive role in maintaining IL-4 mRNA stability in CD4+ T cells via a HuR-mediated mechanism.
Yarovinsky
Timur O
TO
Roy J. and Lucille A. Carver College of Medicine, University of Iowa and Veterans Administration Medical Center, Iowa City, IA 52242, USA. timur-yarovinsky@uiowa.edu
Butler
Noah S
NS
Monick
Martha M
MM
Hunninghake
Gary W
GW
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D015151:Immunoblotting; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D020871:RNA Stability / Q000276:immunology*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015847:Interleukin-4