神经元ELAV样蛋白与肿瘤坏死因子-α信使核糖核酸3'-非翻译区富含尿苷的序列的结合。

Binding of neuronal ELAV-like proteins to the uridine-rich sequence in the 3'-untranslated region of tumor necrosis factor-alpha messenger RNA.

作者信息

Sakai K, Kitagawa Y, Hirose G

机构信息

Department of Neurology, Kanazawa Medical University, Ishikawa, Japan.

出版信息

FEBS Lett. 1999 Mar 5;446(1):157-62. doi: 10.1016/s0014-5793(99)00206-9.

DOI:10.1016/s0014-5793(99)00206-9

PMID:10100634

Abstract

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 implicated in post-transcriptional control of TNF-alpha. In this study, we showed 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 pentanucleotides inside the ARE in the 3'-UTR of TNF-alpha mRNA. The TNF-alpha mRNA-binding region in the protein appears to be identical to the c-myc and IL-3 mRNA-binding regions. Moreover, this study showed that in vitro treatment of neuroblastoma cells with interleukin-4 (IL-4), which inhibits TNF-alpha production, reduced the expression of the neuronal ELAV-like proteins. These results suggest that the expression of neuronal ELAV-like proteins may be closely associated with the expression of TNF-alpha in neuronal cells.

摘要

肿瘤坏死因子-α（TNF-α）是一种促炎细胞因子，参与多种人类中枢神经系统疾病的发病机制。TNF-α mRNA 3'-非翻译区（UTR）中的富含 AU 元件（ARE）与 TNF-α 的转录后调控有关。在本研究中，我们发现一种人类神经元 ELAV 样蛋白可与 TNF-α mRNA 3'-UTR 中的 ARE 结合。该蛋白与 TNF-α mRNA 3'-UTR 中 ARE 内 AUUUA 五核苷酸中的尿苷序列结合。该蛋白中的 TNF-α mRNA 结合区域似乎与 c-myc 和 IL-3 mRNA 结合区域相同。此外，本研究表明，用抑制 TNF-α 产生的白细胞介素-4（IL-4）体外处理神经母细胞瘤细胞，可降低神经元 ELAV 样蛋白的表达。这些结果表明，神经元 ELAV 样蛋白的表达可能与神经元细胞中 TNF-α 的表达密切相关。