4.6 Article

Tristetraprolin binds to the 3′-untranslated region of cyclooxygenase-2 mRNA -: A polyadenylation variant in a cancer cell line lacks the binding site

Journal

JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 278, Issue 16, Pages 13928-13935

Publisher

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M300016200

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Funding

  1. NCI NIH HHS [CA68485, CA77839] Funding Source: Medline
  2. NIGMS NIH HHS [GM15431] Funding Source: Medline

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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 W-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.

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