Abstract
In human colorectal adenocarcinoma cell lines, we found two major transcripts of cyclooxygenase-2, the full-length mRNA and a short polyadenylation variant (2577 kb) lacking the distal segment of the 3'-untranslated region. Tristetraprolin, an mRNA-binding protein that promotes message instability, was shown to bind the cyclooxygenase-2 mRNA in the region of the 3'-untranslated region between nucleotides 3125 and 3432 and to reduce levels of the full-length mRNA. During cell growth and confluence, the expression of tristetraprolin mRNA was inversely correlated with that of the full-length cyclooxygenase-2 transcript, and transfection of tristetraprolin into HCA-7 cells reduced the level of full-length cyclooxygenase-2 mRNA. However, the truncated transcript escaped tristetraprolin binding and downregulation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3' Untranslated Regions
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Base Sequence
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Binding Sites
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Blotting, Northern
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Blotting, Western
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Catalysis
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Cells, Cultured
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Cross-Linking Reagents / pharmacology
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Cyclooxygenase 2
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DNA, Complementary / metabolism
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DNA-Binding Proteins*
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Dose-Response Relationship, Drug
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Down-Regulation
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Endothelium, Vascular / cytology
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Humans
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Immediate-Early Proteins / chemistry*
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Immediate-Early Proteins / metabolism*
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Isoenzymes / chemistry*
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Isoenzymes / metabolism*
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Lipopolysaccharides / pharmacology
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Membrane Proteins
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Molecular Sequence Data
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Polyadenylation
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Precipitin Tests
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Prostaglandin-Endoperoxide Synthases / chemistry*
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Protein Binding
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RNA / metabolism
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RNA, Messenger / metabolism
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Ribonucleases / metabolism
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Time Factors
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Transcription, Genetic
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Transfection
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Tristetraprolin
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Tumor Cells, Cultured
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Umbilical Veins / cytology
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Up-Regulation
Substances
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3' Untranslated Regions
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Cross-Linking Reagents
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DNA, Complementary
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DNA-Binding Proteins
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Immediate-Early Proteins
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Isoenzymes
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Lipopolysaccharides
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Membrane Proteins
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RNA, Messenger
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Tristetraprolin
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ZFP36 protein, human
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RNA
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Ribonucleases