Binding of neuronal ELAV-like proteins to the uridine-rich sequence in the3 '-untranslated region of tumor necrosis factor-alpha messenger RNA

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that is involved in the pathogenesis of several human CNS disorders, The AU-rich element (ARE) in the 3'-untranslated region (UTR) of TNF-alpha mRNA is imp licated in post-transcriptional control of TNF-alpha, In this study, we sho wed that a human neuronal ELAV-like protein binds to the ARE in the 3'-UTR of TNF-alpha mRNA, The protein binds to the uridine stretch in AUUUA pentan ucleotides inside the ARE in the 3'-UTR of TNF-alpha mRNA, The TNF-alpha mR NA-binding region in the protein appears to be identical to the c-myc and I L-3 mRNA-binding regions. Moreover, this study showed that in vitro treatme nt of neuroblastoma cells with interleukin-4 (IL-4), which inhibits TNF-alp ha production, reduced the expression of the neuronal ELAV-like proteins. T hese results suggest that the expression of neuronal ELAV-like proteins may be closely associated with the expression of TNF-alpha in neuronal cells. (C) 1999 Federation of European Biochemical Societies.