IL-1 beta stabilizes COX II mRNA in renal mesangial cells: role of 3'-untranslated region.
We stimulated rat mesangial cells for different time intervals with interleukin-1 beta (IL-1 beta) and phorbol 12-myristate 13-acetate, prepared cytoplasmic extracts, and examined these extracts for the presence of RNA binding proteins by gel mobility shift assays. Here we report that the 3'-untranslated region (3'-UNTR) of the prostaglandin endoperoxide synthase II (COX II) gene is responsible for posttranscriptional regulation of the response to IL-1 beta. Two cytosolic transacting factors of 65 and 45 kDa, respectively, have been detected that bind to the 3'-UNTR. Competition with excess RNA and acid phosphatase treatment of the cytoplasmic extract suggest the binding is specific and that phosphorylation is required for these rapid binding events. These experiments suggest that IL-1 beta induces the phosphorylation of cytosolic factors, which bind to the 3'-UNTR of COX II mRNA, and stabilizes the message.
Srivastava
S K
SK
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Tetsuka
T
T
Daphna-Iken
D
D
Morrison
A R
AR
D000135:Acid Phosphatase / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism*; D004355:Drug Stability; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000135:Acid Phosphatase; D013755:Tetradecanoylphorbol Acetate