Post-transcriptional Regulators in Inflammation: Exploring New Avenues in Biological Therapeutics

Conference paper
Part of the Ernst Schering Foundation Symposium Proceedings book series (SCHERING FOUND, volume 2006/4)

Abstract

The biosynthesis of inflammatory mediators relies on controlling the biogenesis and utilization of their corresponding messenger RNAs (mRNAs). These latter “utilization steps” encompass post-transcriptional mechanisms that gradually and variably impose a series of flexible-rate limiting controls to modify the abundance of an mRNA and the rate of its translation to protein in response to environmental signals. Mechanistically, post-transcriptional machines comprise networks of RNA binding proteins (RBPs), which recognize, passively or inducibly, secondary or tertiary ribonucleotide structures located on their target RNAs. The outcome of these interactions is the stringent control of mRNA maturation, localization, turnover and translation. It is conceivable that if these post-transcriptional interactions fail, they may perturb cellular responses to provide the impetus for chronic disease. Such is the case of the signal-responsive mechanisms affecting inflammatory mRNAs containing the AU-rich family of elements (AREs), which are recognized by a specific subset of RBPs. Intense research in this area has yielded important insight on the specific signals and mechanisms affecting the utilization of ARE-containing mRNAs. Here, we indicate briefly the inflammatory relevance of ARE-related mechanisms to highlight their importance in pathophysiology and their potential in the development of future biological therapies.

Keywords

Cytokine mRNAs Stress Granule Transgenic System mRNA Fate Pyridinyl Imidazole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors wish to thank George Kollias and members of his lab for the collaborative studies on the TNF ARE and its role in immune disease. This work was supported by funding under the Sixth Research Framework Programme of the European Union, Project MUGEN (MUGEN LSHB-CT-2005-005203) and the Hellenic Secretariat for Research and Technology grants PENED-2003-3EΔ770 and PENED-2003-3EΔ264

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • V. Katsanou
    • 1
  • M. Dimitriou
    • 1
  • D. L. Kontoyiannis
    • 1
  1. 1.BSRC “Alexander Fleming”Institute of ImmunologyVariGreece

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