Binding of the ELAV-like protein in murine autoimmune T-cells to the nonameric AU-rich element in the 3' untranslated region of CD154 mRNA.
The CD154 molecule is important for experimental allergic encephalomyelitis (EAE) which is mediated by autoimmune CD4(+) T-cells. Post-transcriptional instabilization/stabilization of mRNAs, which contain an adenylate uridylate rich element (ARE) in their 3' untranslated region (3'UTR), is regulated in part by binding of ARE-binding proteins to the element. We have investigated the protein which binds to the nonameric ARE in the 3'UTR of CD154 mRNA. A protein which binds to the CD154 ARE was found to exist in a extract prepared from murine autoimmune T-cells activated with myelin basic protein (MBP), and turned out to be mHuR which is a ubiquitous ELAV-like protein. It was found that mHuR was upregulated upon stimulation of the T-cells with a MBP antigen. The CD154 ARE and the ARE in the 3'UTR of tumor necrosis factor-alpha (TNF-alpha) mRNA were competed in binding to mHuR, indicating that both AREs bind to the same site on mHuR. The presence of the CD154 ARE downstream of the luciferase cDNA in a reporter plasmid decreased the translational efficiency, and co-expression of the mHuR slightly increased the translation. These results suggest the possibility that the ELAV-like protein participates in the regulation of the expression of CD154 on the autoimmune T-cells. Modification of the expression of CD154 on autoimmune T-cells by regulating the ELAV-like protein may provide effective therapy for EAE and human multiple sclerosis.
Sakai
Koichiro
K
Department of Neurology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-Machi, Kahoku-Gun, Ishikawa 920-0293, Japan.ksakai@kanazawa-med.ac.jp
Kitagawa
Yoko
Y
Saiki
Misuzu
M
Saiki
Shinji
S
Hirose
Genjiro
G
D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D000954:Antigens, Surface; D001327:Autoimmune Diseases / Q000276:immunology*; D001667:Binding, Competitive; D023201:CD40 Ligand / Q000378:metabolism*; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D018076:DNA, Complementary; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; C446766:myelin basic protein 89-101; D023201:CD40 Ligand