Endothelial cytosolic proteins bind to the 3' untranslated region of endothelial nitric oxide synthase mRNA: regulation by tumor necrosis factor alpha.
Changes in endothelial nitric oxide synthase (eNOS) expression may be involved in the endothelium-dependent vasorelaxation dysfunction associated with several vascular diseases. In the present work, we demonstrate that eNOS mRNA contains a previously undescribed cis element in the 3' untranslated region (3' UTR). A U+C-rich segment in the 3' UTR is critical in complex formation with bovine aortic endothelial cell cytosolic proteins. Tumor necrosis factor alpha (TNF-alpha), which destabilizes eNOS mRNA, increased the binding activity of the cytosolic proteins in a time-dependent manner. These data suggest that endothelial cytosolic proteins bind to the 3' UTR of eNOS mRNA. These proteins may play a role in TNF-alpha-induced eNOS mRNA destabilization.
Alonso
J
J
Nephrology, Hypertension and Cardiovascular Research Laboratory, Instituto de Investigaciones Médicas, Fundación Jiménez Díaz, Madrid, Spain.
Sánchez de Miguel
L
L
Montón
M
M
Casado
S
S
López-Farré
A
A
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000201:enzymology; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000235:genetics*; D011131:Polyribonucleotides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011131:Polyribonucleotides; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase