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A constitutive decay element promotes tumor necrosis factor alpha mRNA degradation via an AU-rich element-independent pathway

Stoecklin, G. and Lu, M. and Rattenbacher, B. and Moroni, C.. (2003) A constitutive decay element promotes tumor necrosis factor alpha mRNA degradation via an AU-rich element-independent pathway. Molecular and cellular biology, Vol. 23, H. 10. pp. 3506-3515.

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Official URL: http://edoc.unibas.ch/dok/A5257876

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Abstract

Tumor necrosis factor alpha (TNF-alpha) expression is regulated by transcriptional as well as posttranscriptional mechanisms, the latter including the control of mRNA decay through an AU-rich element (ARE) in the 3' untranslated region (UTR). Using two mutant cell lines deficient for ARE-mediated mRNA decay, we provide evidence for a second element, the constitutive decay element (CDE), which is also located in the 3' UTR of TNF-alpha. In stably transfected RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS), the CDE continues to target a reporter transcript for rapid decay, whereas ARE-mediated decay is blocked. Similarly, the activation of p38 kinase and phosphatidylinositol 3-kinase in NIH 3T3 cells inhibits ARE-mediated but not CDE-mediated mRNA decay. The CDE was mapped to an 80-nucleotide (nt) segment downstream of the ARE, and point mutation analysis identified within the CDE a conserved sequence of 15 nt that is required for decay activity. We propose that the CDE represses TNF-alpha expression by maintaining the mRNA short-lived, thereby preventing excessive induction of TNF-alpha after LPS stimulation. Thus, CDE-mediated mRNA decay is likely to be an important mechanism limiting LPS-induced pathologic processes.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Growth and Development (Moroni)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Growth and Development (Moroni)
UniBasel Contributors:Moroni, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:1098-5549
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:20
Deposited On:22 Mar 2012 13:19

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