TY - JOUR
T1 - Characterization of the binding of the RNA-binding protein AUF1 to te human AT1 receptor mRNA
AU - A., PENDE
AU - M., GIACCHÈ
AU - L., CASTIGLIOLA
AU - L., CONTINI
AU - G., PASSERONE
AU - PATRONE, Mauro
AU - J., D. PORT
AU - G., LOTTI
N1 - Funding Information:
This work was supported in part by MURST grants. We thank Dr. Gary Brewer (Department of Microbiology and Immunology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC) for providing to us the human AUF1 cDNA.
PY - 1999
Y1 - 1999
N2 - An important mechanism of regulation of the expression of the AT1 receptors is the modulation of the mRNA stability. AUF1, a human RNA-binding protein, may play an important role. Since AUF1 seems to bind to AU-rich regions of the 3'-untranslated region of the mRNAs, we verified the nucleotide sequence of human AT1 receptor 3'-untranslated region and we found possible binding sites. In addition we evaluated the expression of the AUF1 protein in human vascular smooth muscle cells: the administration of both isoproterenol and angiotensin II induced a significant increase of total anti-AUF1 immunoreactive isoforms. At the same time angiotensin II induced a significant decrease in the AT1 receptor mRNA abundance. Moreover, we found that recombinant human AUF1 protein binds to human AT1 receptor riboprobes. The protein was able to bind to the distal portion of the 3'-untranslated region, and also to the coding region. Since the clinically relevant AT1 receptor polymorphism is located in the 3'-untranslated region, we created two DNAs, corresponding to the A and C polymorphism, without any differences. Our data demonstrate the presence of AUF1 in human vascular smooth muscle cells and its modulation by activation of the β-adrenergic and the AT1 pathways, a and specific binding of AUF1 to the human AT1 receptor mRNA, suggesting a role of this protein in the modulation of the AT1 receptor expression.
AB - An important mechanism of regulation of the expression of the AT1 receptors is the modulation of the mRNA stability. AUF1, a human RNA-binding protein, may play an important role. Since AUF1 seems to bind to AU-rich regions of the 3'-untranslated region of the mRNAs, we verified the nucleotide sequence of human AT1 receptor 3'-untranslated region and we found possible binding sites. In addition we evaluated the expression of the AUF1 protein in human vascular smooth muscle cells: the administration of both isoproterenol and angiotensin II induced a significant increase of total anti-AUF1 immunoreactive isoforms. At the same time angiotensin II induced a significant decrease in the AT1 receptor mRNA abundance. Moreover, we found that recombinant human AUF1 protein binds to human AT1 receptor riboprobes. The protein was able to bind to the distal portion of the 3'-untranslated region, and also to the coding region. Since the clinically relevant AT1 receptor polymorphism is located in the 3'-untranslated region, we created two DNAs, corresponding to the A and C polymorphism, without any differences. Our data demonstrate the presence of AUF1 in human vascular smooth muscle cells and its modulation by activation of the β-adrenergic and the AT1 pathways, a and specific binding of AUF1 to the human AT1 receptor mRNA, suggesting a role of this protein in the modulation of the AT1 receptor expression.
UR - https://iris.uniupo.it/handle/11579/7544
M3 - Article
SN - 0006-291X
VL - 266
SP - 609
EP - 614
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -