The regulation of the synthesis of the endothelial-derived vasoconstrictor ET-1 (endothelin-1) is a complex process that occurs mainly at the mRNA level. Transcription of the gene accounts for an important part of the regulation of expression, as already described for different modulators such as the cytokine TGF-β (transforming growth factor-β). However, very little is known about mechanisms governing ET-1 expression at the post-transcriptional level. The aim of the present study was to investigate the regulation of the ET-1 expression at this level. Since the 3′-UTR (3′-untranslated region) of mRNAs commonly contains genetic determinants for the post-transcriptional control of gene expression, we focused on the potential role of the 3′-UTR of ET-1 mRNA. Experiments performed with luciferase reporter constructs containing the 3′-UTR showed that this region exerts a potent destabilizing effect. Deletional analyses allowed us to locate this activity within a region at positions 924–1127. Some (but not all) of the AREs (AU-rich elements) present in this region were found to be essential for this mRNA-destabilizing activity. We also present evidence that cytosolic proteins from endothelial cells interact specifically with these RNA elements, and that a close correlation exists between the ability of the AREs to destabilize ET-1 mRNA and the binding of proteins to these elements. Our results are compatible with the existence of a strong repressional control of ET-1 expression mediated by destabilization of the mRNA exerted through the interaction of specific cytosolic proteins with AREs present in the 3′-UTR of the gene.
Skip Nav Destination
Article navigation
May 2005
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
April 26 2005
Endothelin-1 expression is strongly repressed by AU-rich elements in the 3′-untranslated region of the gene
Francisco M. REIMUNDE;
Francisco M. REIMUNDE
1Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas, C.S.I.C., Instituto “Reina Sofía” de Investigaciones Nefrológicas and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Ramiro de Maeztu 9, E-28040, Madrid, Spain
Search for other works by this author on:
Cristina CASTAÑARES;
Cristina CASTAÑARES
1Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas, C.S.I.C., Instituto “Reina Sofía” de Investigaciones Nefrológicas and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Ramiro de Maeztu 9, E-28040, Madrid, Spain
Search for other works by this author on:
Mariano REDONDO-HORCAJO;
Mariano REDONDO-HORCAJO
1Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas, C.S.I.C., Instituto “Reina Sofía” de Investigaciones Nefrológicas and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Ramiro de Maeztu 9, E-28040, Madrid, Spain
Search for other works by this author on:
Santiago LAMAS;
Santiago LAMAS
1Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas, C.S.I.C., Instituto “Reina Sofía” de Investigaciones Nefrológicas and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Ramiro de Maeztu 9, E-28040, Madrid, Spain
Search for other works by this author on:
Fernando RODRÍGUEZ-PASCUAL
Fernando RODRÍGUEZ-PASCUAL
1
1Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas, C.S.I.C., Instituto “Reina Sofía” de Investigaciones Nefrológicas and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Ramiro de Maeztu 9, E-28040, Madrid, Spain
1To whom correspondence should be addressed (email frodriguez@cib.csic.es).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
October 05 2004
Revision Received:
December 09 2004
Accepted:
December 14 2004
Accepted Manuscript online:
December 14 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 387 (3): 763–772.
Article history
Received:
October 05 2004
Revision Received:
December 09 2004
Accepted:
December 14 2004
Accepted Manuscript online:
December 14 2004
Citation
Francisco M. REIMUNDE, Cristina CASTAÑARES, Mariano REDONDO-HORCAJO, Santiago LAMAS, Fernando RODRÍGUEZ-PASCUAL; Endothelin-1 expression is strongly repressed by AU-rich elements in the 3′-untranslated region of the gene. Biochem J 1 May 2005; 387 (3): 763–772. doi: https://doi.org/10.1042/BJ20041687
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.