This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stoecklin, G.
Right arrow Articles by Moroni, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stoecklin, G.
Right arrow Articles by Moroni, C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2003, p. 3506-3515, Vol. 23, No. 10
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.10.3506-3515.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Constitutive Decay Element Promotes Tumor Necrosis Factor Alpha mRNA Degradation via an AU-Rich Element-Independent Pathway

Georg Stoecklin,{dagger} Min Lu, Bernd Rattenbacher, and Christoph Moroni*

Institute of Medical Microbiology, University of Basel, 4003 Basel, Switzerland

Received 5 November 2002/ Returned for modification 12 December 2002/ Accepted 18 February 2003

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.

* Corresponding author. Mailing address: Christoph Moroni Institute of Medical Microbiology, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland. Phone: 41 61 267 32 64. Fax: 41 61 267 32 83. E-mail: christoph.moroni{at}unibas.ch.

{dagger} Present address: Division of Rheumatology and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.

Molecular and Cellular Biology, May 2003, p. 3506-3515, Vol. 23, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.10.3506-3515.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lin, S. L., Castano, A. P., Nowlin, B. T., Lupher, M. L. Jr., Duffield, J. S. (2009). Bone Marrow Ly6Chigh Monocytes Are Selectively Recruited to Injured Kidney and Differentiate into Functionally Distinct Populations. J. Immunol. 183: 6733-6743 [Abstract] [Full Text]  
  • Sinsimer, K. S., Gratacos, F. M., Knapinska, A. M., Lu, J., Krause, C. D., Wierzbowski, A. V., Maher, L. R., Scrudato, S., Rivera, Y. M., Gupta, S., Turrin, D. K., De La Cruz, M. P., Pestka, S., Brewer, G. (2008). Chaperone Hsp27, a Novel Subunit of AUF1 Protein Complexes, Functions in AU-Rich Element-Mediated mRNA Decay. Mol. Cell. Biol. 28: 5223-5237 [Abstract] [Full Text]  
  • Chen, G., Guo, X., Lv, F., Xu, Y., Gao, G. (2008). p72 DEAD box RNA helicase is required for optimal function of the zinc-finger antiviral protein. Proc. Natl. Acad. Sci. USA 105: 4352-4357 [Abstract] [Full Text]  
  • Skinner, S. J., Deleault, K. M., Fecteau, R., Brooks, S. A. (2008). Extracellular Signal-regulated Kinase Regulation of Tumor Necrosis Factor-{alpha} mRNA Nucleocytoplasmic Transport Requires TAP-NxT1 Binding and the AU-rich Element. J. Biol. Chem. 283: 3191-3199 [Abstract] [Full Text]  
  • Garneau, N. L., Sokoloski, K. J., Opyrchal, M., Neff, C. P., Wilusz, C. J., Wilusz, J. (2008). The 3' Untranslated Region of Sindbis Virus Represses Deadenylation of Viral Transcripts in Mosquito and Mammalian Cells. J. Virol. 82: 880-892 [Abstract] [Full Text]  
  • Guo, X., Ma, J., Sun, J., Gao, G. (2007). The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA. Proc. Natl. Acad. Sci. USA 104: 151-156 [Abstract] [Full Text]  
  • Paschoud, S., Dogar, A. M., Kuntz, C., Grisoni-Neupert, B., Richman, L., Kuhn, L. C. (2006). Destabilization of Interleukin-6 mRNA Requires a Putative RNA Stem-Loop Structure, an AU-Rich Element, and the RNA-Binding Protein AUF1. Mol. Cell. Biol. 26: 8228-8241 [Abstract] [Full Text]  
  • Wang, J. G., Collinge, M., Ramgolam, V., Ayalon, O., Fan, X. C., Pardi, R., Bender, J. R. (2006). LFA-1-Dependent HuR Nuclear Export and Cytokine mRNA Stabilization in T Cell Activation. J. Immunol. 176: 2105-2113 [Abstract] [Full Text]  
  • Cheong, R., Bergmann, A., Werner, S. L., Regal, J., Hoffmann, A., Levchenko, A. (2006). Transient I{kappa}B Kinase Activity Mediates Temporal NF-{kappa}B Dynamics in Response to a Wide Range of Tumor Necrosis Factor-{alpha} Doses. J. Biol. Chem. 281: 2945-2950 [Abstract] [Full Text]  
  • Novotny, M., Datta, S., Biswas, R., Hamilton, T. (2005). Functionally Independent AU-rich Sequence Motifs Regulate KC (CXCL1) mRNA. J. Biol. Chem. 280: 30166-30174 [Abstract] [Full Text]  
  • Anderson, P., Phillips, K., Stoecklin, G., Kedersha, N. (2004). Post-transcriptional regulation of proinflammatory proteins. J. Leukoc. Biol. 76: 42-47 [Abstract] [Full Text]  
  • Benjamin, D., Colombi, M., Moroni, C. (2004). A GFP-based assay for rapid screening of compounds affecting ARE-dependent mRNA turnover. Nucleic Acids Res 32: e89-e89 [Abstract] [Full Text]  
  • Brooks, S. A., Connolly, J. E., Rigby, W. F. C. (2004). The Role of mRNA Turnover in the Regulation of Tristetraprolin Expression: Evidence for an Extracellular Signal-Regulated Kinase-Specific, AU-Rich Element-Dependent, Autoregulatory Pathway. J. Immunol. 172: 7263-7271 [Abstract] [Full Text]  
  • Winzen, R., Gowrishankar, G., Bollig, F., Redich, N., Resch, K., Holtmann, H. (2004). Distinct Domains of AU-Rich Elements Exert Different Functions in mRNA Destabilization and Stabilization by p38 Mitogen-Activated Protein Kinase or HuR. Mol. Cell. Biol. 24: 4835-4847 [Abstract] [Full Text]  
  • Wilson, G. M., Lu, J., Sutphen, K., Sun, Y., Huynh, Y., Brewer, G. (2003). Regulation of A + U-rich Element-directed mRNA Turnover Involving Reversible Phosphorylation of AUF1. J. Biol. Chem. 278: 33029-33038 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»