Post-transcriptional Control of Cyclooxygenase-2 Gene Expression

The cyclooxygenase (COX)-2 enzyme is responsible for increased prostaglandin formation in inflammatory states and is the major target of nonsteroidal anti-inflammatory drugs. Normally COX-2 expression is tightly regulated, however, constitutive overexpression plays a key role in colon carcinogenesis. To understand the mechanisms controlling COX-2 expression, we examined the ability of the 3′-untranslated region of the COX-2 mRNA to regulate post-transcriptional events. When fused to a reporter gene, the 3′-untranslated region mediated rapid mRNA decay (t 1 2 = 30 min), which was comparable to endogenous COX-2 mRNA turnover in serum-induced fibroblasts treated with actinomycin D or dexamethasone. Deletion analysis demonstrated that a conserved 116-nucleotide AU-rich sequence element (ARE) mediated mRNA degradation. In transiently transfected cells, this region inhibited protein synthesis approximately 3-fold. However, this inhibition did not occur through changes in mRNA stability since mRNA half-life and steady-state mRNA levels were unchanged. RNA mobility shift assays demonstrated a complex of cytoplasmic proteins that bound specifically to the ARE, and UV cross-linking studies identified proteins ranging from 90 to 35 kDa. Fractionation of the cytosol showed differential association of ARE-binding proteins to polysomes and S130 fractions. We propose that these factors influence expression at a post-transcriptional step and, if dysregulated, may increase COX-2 protein as detected in colon cancer.

• Publication year

  2000

• Venue

  Journal of Biological Chemistry

• Publication date

  2000-04-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.275.16.11750PMID 10766797
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Cytoplasmic ARE-binding proteins bound specifically to the AU-rich sequence element, and cytosolic fractionation showed differential association with polysomes and S130 fractions.

  Confidence 0.93

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• In transiently transfected cells, the AU-rich sequence element inhibited protein synthesis about threefold without changing mRNA half-life or steady-state mRNA levels.

  Confidence 0.95

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• A conserved 116-nucleotide AU-rich sequence element within the COX-2 3' untranslated region mediated mRNA degradation.

  Confidence 0.97

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• The COX-2 3' untranslated region mediated rapid mRNA decay with a half-life of about 30 minutes.

  Confidence 0.98

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review

• are-binding proteins

  RNA-binding protein

  Proteins that interact with AU-rich RNA elements in the cytoplasm.

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• au-rich sequence element

  regulatory RNA element

  A conserved 116-nucleotide AU-rich segment within the COX-2 3' untranslated region.

  Aliases: ARE

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• cox-2 3' untranslated region

  RNA region

  The noncoding region at the 3' end of COX-2 mRNA.

  Aliases: 3'-untranslated region of the COX-2 mRNA

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• mrna decay

  biological process

  The degradation and turnover of messenger RNA molecules.

  Aliases: mRNA degradation, mRNA turnover

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• mrna stability

  molecular property

  The persistence or half-life of an mRNA molecule.

  Aliases: mRNA half-life

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• polysomes

  ribonucleoprotein complex

  Complexes of a single mRNA with multiple ribosomes during translation.

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• protein synthesis

  biological process

  The cellular production of protein from mRNA templates.

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review
• s130 fractions

  cell fraction

  A post-ribosomal cytosolic fraction obtained after polysome removal.

  Aliases: S130

  뀨 (7c402c1b98) extractionAll you need is Python (5d7gwfm5zu) review박진우 (dztg5apj7m) review

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