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.

Next Article 

Molecular and Cellular Biology, June 2000, p. 3753-3763, Vol. 20, No. 11
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Somatic mRNA Turnover Mutants Implicate Tristetraprolin in the Interleukin-3 mRNA Degradation Pathway

Georg Stoecklin, Xiu-Fen Ming, Renate Looser, and Christoph Moroni*

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

Received 16 December 1999/Returned for modification 25 January 2000/Accepted 8 March 2000

Control of mRNA stability is critical for expression of short-lived transcripts from cytokines and proto-oncogenes. Regulation involves an AU-rich element (ARE) in the 3' untranslated region (3'UTR) and cognate trans-acting factors thought to promote either degradation or stabilization of the mRNA. In this study we present a novel approach using somatic cell genetics designed to identify regulators of interleukin-3 (IL-3) mRNA turnover. Mutant cell lines were generated from diploid HT1080 cells transfected with a reporter construct containing green fluorescent protein (GFP) linked to the IL-3 3'UTR. GFP was expressed at low levels due to rapid decay of the mRNA. Following chemical mutagenesis and selection of GFP-overexpressing cells, we could isolate three mutant clones (slowA, slowB, and slowC) with a specific, trans-acting defect in IL-3 mRNA degradation, while the stability of IL-2 and tumor necrosis factor alpha reporter transcripts was not affected. Somatic cell fusion experiments revealed that the mutants are genetically recessive and form two complementation groups. Expression of the tristetraprolin gene in both groups led to reversion of the mutant phenotype, thereby linking this gene to the IL-3 mRNA degradation pathway. The genetic approach described here should allow identification of the defective functions by gene transfer and is also applicable to the study of other mRNA turnover pathways.


* Corresponding author. Mailing address: Institute of Medical Microbiology, University of Basel, Petersplatz 10, CH 4003, Basel, Switzerland. Phone: 41 61 2673264. Fax: 41 61 2673298. E-mail: christoph.moroni{at}unibas.ch.


Molecular and Cellular Biology, June 2000, p. 3753-3763, Vol. 20, No. 11
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Ogilvie, R. L., SternJohn, J. R., Rattenbacher, B., Vlasova, I. A., Williams, D. A., Hau, H. H., Blackshear, P. J., Bohjanen, P. R. (2009). Tristetraprolin Mediates Interferon-{gamma} mRNA Decay. J. Biol. Chem. 284: 11216-11223 [Abstract] [Full Text]  
  • Rowlett, R. M., Chrestensen, C. A., Schroeder, M. J., Harp, M. G., Pelo, J. W., Shabanowitz, J., DeRose, R., Hunt, D. F., Sturgill, T. W., Worthington, M. T. (2008). Inhibition of tristetraprolin deadenylation by poly(A) binding protein. Am. J. Physiol. Gastrointest. Liver Physiol. 295: G421-G430 [Abstract] [Full Text]  
  • Jalonen, U., Paukkeri, E.-L., Moilanen, E. (2008). Compounds That Increase or Mimic Cyclic Adenosine Monophosphate Enhance Tristetraprolin Degradation in Lipopolysaccharide-Treated Murine J774 Macrophages. J. Pharmacol. Exp. Ther. 326: 514-522 [Abstract] [Full Text]  
  • Emmons, J., Townley-Tilson, W.H. D., Deleault, K. M., Skinner, S. J., Gross, R. H., Whitfield, M. L., Brooks, S. A. (2008). Identification of TTP mRNA targets in human dendritic cells reveals TTP as a critical regulator of dendritic cell maturation. RNA 14: 888-902 [Abstract] [Full Text]  
  • Stoecklin, G., Tenenbaum, S. A., Mayo, T., Chittur, S. V., George, A. D., Baroni, T. E., Blackshear, P. J., Anderson, P. (2008). Genome-wide Analysis Identifies Interleukin-10 mRNA as Target of Tristetraprolin. J. Biol. Chem. 283: 11689-11699 [Abstract] [Full Text]  
  • Patil, C.S., Kirkwood, K.L. (2007). p38 MAPK Signaling in Oral-related Diseases. JDR 86: 812-825 [Abstract] [Full Text]  
  • Chang, X., Fan, Y., Karyala, S., Schwemberger, S., Tomlinson, C. R., Sartor, M. A., Puga, A. (2007). Ligand-Independent Regulation of Transforming Growth Factor {beta}1 Expression and Cell Cycle Progression by the Aryl Hydrocarbon Receptor. Mol. Cell. Biol. 27: 6127-6139 [Abstract] [Full Text]  
  • Frasca, D., Landin, A. M., Alvarez, J. P., Blackshear, P. J., Riley, R. L., Blomberg, B. B. (2007). Tristetraprolin, a Negative Regulator of mRNA Stability, Is Increased in Old B Cells and Is Involved in the Degradation of E47 mRNA. J. Immunol. 179: 918-927 [Abstract] [Full Text]  
  • Franks, T. M., Lykke-Andersen, J. (2007). TTP and BRF proteins nucleate processing body formation to silence mRNAs with AU-rich elements. Genes Dev. 21: 719-735 [Abstract] [Full Text]  
  • Sun, L., Stoecklin, G., Van Way, S., Hinkovska-Galcheva, V., Guo, R.-F., Anderson, P., Shanley, T. P. (2007). Tristetraprolin (TTP)-14-3-3 Complex Formation Protects TTP from Dephosphorylation by Protein Phosphatase 2a and Stabilizes Tumor Necrosis Factor-{alpha} mRNA. J. Biol. Chem. 282: 3766-3777 [Abstract] [Full Text]  
  • Benjamin, D., Schmidlin, M., Min, L., Gross, B., Moroni, C. (2006). BRF1 Protein Turnover and mRNA Decay Activity Are Regulated by Protein Kinase B at the Same Phosphorylation Sites. Mol. Cell. Biol. 26: 9497-9507 [Abstract] [Full Text]  
  • Smoak, K., Cidlowski, J. A. (2006). Glucocorticoids Regulate Tristetraprolin Synthesis and Posttranscriptionally Regulate Tumor Necrosis Factor Alpha Inflammatory Signaling. Mol. Cell. Biol. 26: 9126-9135 [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]  
  • Newman, E. A., Muh, S. J., Hovhannisyan, R. H., Warzecha, C. C., Jones, R. B., McKeehan, W. L., Carstens, R. P. (2006). Identification of RNA-binding proteins that regulate FGFR2 splicing through the use of sensitive and specific dual color fluorescence minigene assays. RNA 12: 1129-1141 [Abstract] [Full Text]  
  • Lu, J.-Y., Bergman, N., Sadri, N., Schneider, R. J. (2006). Assembly of AUF1 with eIF4G-poly(A) binding protein complex suggests a translation function in AU-rich mRNA decay. RNA 12: 883-893 [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]  
  • Barreau, C., Paillard, L., Osborne, H. B. (2006). AU-rich elements and associated factors: are there unifying principles?. Nucleic Acids Res 33: 7138-7150 [Abstract] [Full Text]  
  • Linker, K., Pautz, A., Fechir, M., Hubrich, T., Greeve, J., Kleinert, H. (2005). Involvement of KSRP in the post-transcriptional regulation of human iNOS expression-complex interplay of KSRP with TTP and HuR. Nucleic Acids Res 33: 4813-4827 [Abstract] [Full Text]  
  • Pascale, A., Amadio, M., Scapagnini, G., Lanni, C., Racchi, M., Provenzani, A., Govoni, S., Alkon, D. L., Quattrone, A. (2005). Neuronal ELAV proteins enhance mRNA stability by a PKC{alpha}-dependent pathway. Proc. Natl. Acad. Sci. USA 102: 12065-12070 [Abstract] [Full Text]  
  • Paillusson, A., Hirschi, N., Vallan, C., Azzalin, C. M., Muhlemann, O. (2005). A GFP-based reporter system to monitor nonsense-mediated mRNA decay. Nucleic Acids Res 33: e54-e54 [Abstract] [Full Text]  
  • Ogilvie, R. L., Abelson, M., Hau, H. H., Vlasova, I., Blackshear, P. J., Bohjanen, P. R. (2005). Tristetraprolin Down-Regulates IL-2 Gene Expression through AU-Rich Element-Mediated mRNA Decay. J. Immunol. 174: 953-961 [Abstract] [Full Text]  
  • Groger, M., Loewe, R., Holnthoner, W., Embacher, R., Pillinger, M., Herron, G. S., Wolff, K., Petzelbauer, P. (2004). IL-3 Induces Expression of Lymphatic Markers Prox-1 and Podoplanin in Human Endothelial Cells. J. Immunol. 173: 7161-7169 [Abstract] [Full Text]  
  • Tchen, C. R., Brook, M., Saklatvala, J., Clark, A. R. (2004). The Stability of Tristetraprolin mRNA Is Regulated by Mitogen-activated Protein Kinase p38 and by Tristetraprolin Itself. J. Biol. Chem. 279: 32393-32400 [Abstract] [Full Text]  
  • Lu, J.-Y., Schneider, R. J. (2004). Tissue Distribution of AU-rich mRNA-binding Proteins Involved in Regulation of mRNA Decay. J. Biol. Chem. 279: 12974-12979 [Abstract] [Full Text]  
  • Chrestensen, C. A., Schroeder, M. J., Shabanowitz, J., Hunt, D. F., Pelo, J. W., Worthington, M. T., Sturgill, T. W. (2004). MAPKAP Kinase 2 Phosphorylates Tristetraprolin on in Vivo Sites Including Ser178, a Site Required for 14-3-3 Binding. J. Biol. Chem. 279: 10176-10184 [Abstract] [Full Text]  
  • Raineri, I., Wegmueller, D., Gross, B., Certa, U., Moroni, C. (2004). Roles of AUF1 isoforms, HuR and BRF1 in ARE-dependent mRNA turnover studied by RNA interference. Nucleic Acids Res 32: 1279-1288 [Abstract] [Full Text]  
  • Twizere, J.-C., Kruys, V., Lefebvre, L., Vanderplasschen, A., Collete, D., Debacq, C., Lai, W. S., Jauniaux, J.-C., Bernstein, L. R., Semmes, O. J., Burny, A., Blackshear, P. J., Kettmann, R., Willems, L. (2003). Interaction of Retroviral Tax Oncoproteins With Tristetraprolin and Regulation of Tumor Necrosis Factor-{alpha} Expression. JNCI J Natl Cancer Inst 95: 1846-1859 [Abstract] [Full Text]  
  • Park-Lee, S., Kim, S., Laird-Offringa, I. A. (2003). Characterization of the Interaction between Neuronal RNA-binding Protein HuD and AU-rich RNA. J. Biol. Chem. 278: 39801-39808 [Abstract] [Full Text]  
  • Ji, B., Chen, X.-q., Misek, D. E., Kuick, R., Hanash, S., Ernst, S., Najarian, R., Logsdon, C. D. (2003). Pancreatic gene expression during the initiation of acute pancreatitis: identification of EGR-1 as a key regulator. Physiol. Genomics 14: 59-72 [Abstract] [Full Text]  
  • Stoecklin, G., Lu, M., Rattenbacher, B., Moroni, C. (2003). A Constitutive Decay Element Promotes Tumor Necrosis Factor Alpha mRNA Degradation via an AU-Rich Element-Independent Pathway. Mol. Cell. Biol. 23: 3506-3515 [Abstract] [Full Text]  
  • Frevel, M. A. E., Bakheet, T., Silva, A. M., Hissong, J. G., Khabar, K. S. A., Williams, B. R. G. (2003). p38 Mitogen-Activated Protein Kinase-Dependent and -Independent Signaling of mRNA Stability of AU-Rich Element-Containing Transcripts. Mol. Cell. Biol. 23: 425-436 [Abstract] [Full Text]  
  • Korhonen, R., Lahti, A., Hamalainen, M., Kankaanranta, H., Moilanen, E. (2002). Dexamethasone Inhibits Inducible Nitric-Oxide Synthase Expression and Nitric Oxide Production by Destabilizing mRNA in Lipopolysaccharide-Treated Macrophages. Mol. Pharmacol. 62: 698-704 [Abstract] [Full Text]  
  • Laroia, G., Schneider, R. J. (2002). Alternate exon insertion controls selective ubiquitination and degradation of different AUF1 protein isoforms. Nucleic Acids Res 30: 3052-3058 [Abstract] [Full Text]  
  • Chinn, A. M., Ciais, D., Bailly, S., Chambaz, E., LaMarre, J., Feige, J.-J. (2002). Identification of Two Novel ACTH-Responsive Genes Encoding Manganese-Dependent Superoxide Dismutase (SOD2) and the Zinc Finger Protein TIS11b [Tetradecanoyl Phorbol Acetate (TPA)-Inducible Sequence 11b]. Mol. Endocrinol. 16: 1417-1427 [Abstract] [Full Text]  
  • MacKenzie, S., Fernandez-Troy, N., Espel, E. (2002). Post-transcriptional regulation of TNF-{alpha} during in vitro differentiation of human monocytes/macrophages in primary culture. J. Leukoc. Biol. 71: 1026-1032 [Abstract] [Full Text]  
  • Phillips, R. S., Ramos, S. B. V., Blackshear, P. J. (2002). Members of the Tristetraprolin Family of Tandem CCCH Zinc Finger Proteins Exhibit CRM1-dependent Nucleocytoplasmic Shuttling. J. Biol. Chem. 277: 11606-11613 [Abstract] [Full Text]  
  • Carballo, E., Cao, H., Lai, W. S., Kennington, E. A., Campbell, D., Blackshear, P. J. (2001). Decreased Sensitivity of Tristetraprolin-deficient Cells to p38 Inhibitors Suggests the Involvement of Tristetraprolin in the p38 Signaling Pathway. J. Biol. Chem. 276: 42580-42587 [Abstract] [Full Text]  
  • Mahtani, K. R., Brook, M., Dean, J. L. E., Sully, G., Saklatvala, J., Clark, A. R. (2001). Mitogen-Activated Protein Kinase p38 Controls the Expression and Posttranslational Modification of Tristetraprolin, a Regulator of Tumor Necrosis Factor Alpha mRNA Stability. Mol. Cell. Biol. 21: 6461-6469 [Abstract] [Full Text]  
  • Ming, X.-F., Stoecklin, G., Lu, M., Looser, R., Moroni, C. (2001). Parallel and Independent Regulation of Interleukin-3 mRNA Turnover by Phosphatidylinositol 3-Kinase and p38 Mitogen-Activated Protein Kinase. Mol. Cell. Biol. 21: 5778-5789 [Abstract] [Full Text]  
  • Bakheet, T., Frevel, M., Williams, B. R. G., Greer, W., Khabar, K. S. A. (2001). ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins. Nucleic Acids Res 29: 246-254 [Abstract] [Full Text]  
  • Johnson, M. A., Pérez-Amador, M. A., Lidder, P., Green, P. J. (2000). Mutants of Arabidopsis defective in a sequence-specific mRNA degradation pathway. Proc. Natl. Acad. Sci. USA 10.1073/pnas.240354097v1 [Abstract] [Full Text]  
  • Lai, W. S., Blackshear, P. J. (2001). Interactions of CCCH Zinc Finger Proteins with mRNA. TRISTETRAPROLIN-MEDIATED AU-RICH ELEMENT-DEPENDENT mRNA DEGRADATION CAN OCCUR IN THE ABSENCE OF A POLY(A) TAIL. J. Biol. Chem. 276: 23144-23154 [Abstract] [Full Text]  
  • Laroia, G., Sarkar, B., Schneider, R. J. (2002). Ubiquitin-dependent mechanism regulates rapid turnover of AU-rich cytokine mRNAs. Proc. Natl. Acad. Sci. USA 99: 1842-1846 [Abstract] [Full Text]  
  • Johnson, M. A., Perez-Amador, M. A., Lidder, P., Green, P. J. (2000). Mutants of Arabidopsis defective in a sequence-specific mRNA degradation pathway. Proc. Natl. Acad. Sci. USA 97: 13991-13996 [Abstract] [Full Text]