AT1receptor activation leads to vasoconstriction, blood pressure increase, free radical release, and cell growth. AT1receptor regulation contributes to the adaptation of the renin-angiotensin system to long-term stimulation and serves as explanation for the involvement of the AT1receptor in the pathogenesis of cardiovascular disease. The molecular mechanisms involved in AT1receptor regulation are poorly understood. Here, we report that angiotensin II accelerates AT1receptor 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 AT1receptor mRNA. Sequential protein purifications led to the discovery of a novel mRNA binding protein, calreticulin, which mediates destabilization of the AT1receptor mRNA. Angiotensin II–caused phosphorylation of calreticulin enables binding of calreticulin to the AT1receptor mRNA at bases 2175 to 2195 and propagates calreticulin-induced acceleration of AT1receptor mRNA decay. Thus, a novel mRNA binding protein, calreticulin, is discovered, which causes AT1receptor mRNA degradation via binding to a distinct mRNA region in the 3′ untranslated region. These findings display a novel mechanism of posttranscriptional mRNA processing.