Tumor necrosis factor-alpha mRNA remains unstable and hypoadenylated upon stimulation of macrophages by lipopolysaccharides
| Autor: | T, Mijatovic, L, Houzet, P, Defrance, L, Droogmans, G, Huez, V, Kruys |
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| Rok vydání: | 2000 |
| Předmět: |
Lipopolysaccharides
Tumor Necrosis Factor-alpha Macrophages Proteins Zinc Fingers Macrophage Activation Cell Line Feedback Immediate-Early Proteins DNA-Binding Proteins Mice Cytosol Gene Expression Regulation Tristetraprolin Protein Biosynthesis Animals Humans RNA Messenger 3' Untranslated Regions Half-Life HeLa Cells |
| Zdroj: | European journal of biochemistry. 267(19) |
| ISSN: | 0014-2956 |
| Popis: | TNF-alpha gene expression is regulated at transcriptional and post-transcriptional levels in mouse macrophages. The post-transcriptional regulation is mediated by the AU-rich element (ARE) located in the TNF-alpha mRNA 3' untranslated region (UTR), which controls its translation and stability. In resting macrophages, the ARE represses TNF-alpha mRNA translation. Activation of macrophages with various agents [for example lipopolysaccharide (LPS), viruses] results in translational derepression, leading to the production of high levels of TNF-alpha. TNF-alpha ARE has also been shown to confer mRNA instability as its deletion from the mouse genome leads to an increase in the TNF-alpha mRNA half-life [Kontoyiannis, D., Pasparakis, M., Pizzaro, T., Cominelli, F.Kollias, G. (1999) Immunity 10, 387-398]. In this study, we measured the half-life as well as the poly(A) tail length of TNF-alpha mRNA in the course of macrophage activation by LPS. We report that TNF-alpha mRNA is short lived even in conditions of maximal TNF-alpha synthesis. Moreover, TNF-alpha mRNA is hypoadenylated in a constitutive manner. These results reveal that TNF-alpha mRNA rapid turnover does not constitute a regulatory step of TNF-alpha biosynthesis in macrophages and that TNF-alpha mRNA translational activation upon LPS stimulation is not accompanied by a change of poly(A) tail length. |
| Databáze: | OpenAIRE |
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