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Circulation Research. 2002;90:53-58
Published online before print November 26, 2001, doi: 10.1161/hh0102.102503
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(Circulation Research. 2002;90:53.)
© 2002 American Heart Association, Inc.

Molecular Medicine

Destabilization of AT1 Receptor mRNA by Calreticulin

Georg Nickenig*, Frank Michaelsen*, Cornelius Müller, Anja Berger, Thomas Vogel, Agapios Sachinidis, Hans Vetter, Michael Böhm

From Klinik und Poliklinik Innere Medizin III (G.N., F.M., C.M., A.B., T.V., M.B.), Universität des Saarlandes, Homburg, Germany; Institut für Physiologie (A.S.), Universität zu Köln, Germany; and Medizinische Poliklinik (H.V.), Universität Bonn, Germany.

Correspondence to Dr Georg Nickenig, Klinik Innere Medizin III, Universität des Saarlandes, 66421 Homburg, Germany. E-mail nickenig{at}med-in.uni-sb.de

AT1 receptor activation leads to vasoconstriction, blood pressure increase, free radical release, and cell growth. AT1 receptor regulation contributes to the adaptation of the renin-angiotensin system to long-term stimulation and serves as explanation for the involvement of the AT1 receptor in the pathogenesis of cardiovascular disease. The molecular mechanisms involved in AT1 receptor regulation are poorly understood. Here, we report that angiotensin II accelerates AT1 receptor mRNA decay in vascular smooth muscle cells. A cognate mRNA region within the 3' untranslated region at bases 2175 to 2195 governs the inducible decay of the AT1 receptor mRNA. Sequential protein purifications led to the discovery of a novel mRNA binding protein, calreticulin, which mediates destabilization of the AT1 receptor mRNA. Angiotensin II–caused phosphorylation of calreticulin enables binding of calreticulin to the AT1 receptor mRNA at bases 2175 to 2195 and propagates calreticulin-induced acceleration of AT1 receptor mRNA decay. Thus, a novel mRNA binding protein, calreticulin, is discovered, which causes AT1 receptor mRNA degradation via binding to a distinct mRNA region in the 3' untranslated region. These findings display a novel mechanism of posttranscriptional mRNA processing.


Key Words: angiotensin II • AT1 receptor • mRNA binding protein • mRNA stability • calreticulin




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