Post-transcriptional regulation of cytokine genes in fish: A role for conserved AU-rich elements located in the 3 '-untranslated region of their mRNAs

Francisco J. Roca, Maria L. Cayuela, Chris J. Secombes, Jose Meseguer, Victoriano Mulero

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The overproduction of cytokines, such us interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha), contributes to the pathological complications observed in many inflammatory diseases caused by bacterial endotoxins. The synthesis of these cytokines is tightly regulated at both transcriptional and post-transcriptional levels. Post-transcriptional regulation of gene expression depends on specific cis-acting sequences and trans-acting factors. Thus, the presence of adenylate- and uridylate-rich (AU-rich) elements (AREs) has been described in the 3'-untranslated regions (UTRs) of many unstable mammalian mRNAs. Although, it represents the most widespread, phylogenetically conserved and efficient determinant of mRNA stability among those so far characterized in mammalian cells, no studies are available on the functional relevance of this sequence in non-mammalian vertebrates. In this contribution, we study the enzymatic activity of various luciferase reporter constructs, containing or lacking the 3'UTR of IL-1 beta and TNF alpha from different fish species, and report the finding that bony fish AREs are able to decrease luciferase activity but are less potent than their mammalian counterparts. Surprisingly, the 3'UTR of the IL-1 beta from the cartilaginous fish small spotted catshark had the greatest ability to decrease luciferase activity. Lastly, the functional significance of the above was confirmed by measuring the half-life of IL-1 beta and TNF alpha mRNAs in gilthead seabream leukocytes by blocking transcription with actinomycin D. Both cytokine mRNAs were unstable with an estimated half-life of about 45 min in control and activated cells. (c) 2006 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)472-478
Number of pages7
JournalMolecular Immunology
Volume44
Issue number4
Early online date3 Apr 2006
DOIs
Publication statusPublished - Jan 2007

Keywords

  • interleukin-1 beta
  • tumor necrosis factor alpha
  • ARE
  • mRNA stability
  • phylogeny
  • fish
  • necrosis-factor-alpha
  • 3 untranslated region
  • zinc-finger proteins
  • tristetraprolin
  • degradation
  • biosynthesis
  • expression
  • complexes
  • promotes

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