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More MS news articles for April 2003

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

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12686504&dopt=Abstract

Mol Immunol 2003 May;39(14):879-83
Sakai K, Kitagawa Y, Saiki M, Saiki S, Hirose G.
Department of Neurology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-Machi, Kahoku-Gun, 920-0293, Ishikawa, Japan

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.