Regulator of G protein signaling 4 (RGS4) regulates the strength and duration of 
G protein signaling and plays an important role in smooth muscle contraction, 
cardiac development, and psychiatric disorders. Little is known about the 
posttranscriptional regulation of RGS4 expression. We cloned the full-length 
cDNA of rabbit RGS4, which contains a long 3'-untranslated region (UTR) with 
several AU-rich elements (AREs). We determined whether RGS4 mRNA stability is 
mediated by the RNA-binding protein human antigen R (HuR) and contributes to 
IL-1β-induced upregulation of RGS4 expression. We show that IL-1β treatment in 
colonic smooth muscle cells doubled the half-life of RGS4 mRNA. Addition of RGS4 
3'-UTR to the downstream of Renilla luciferase reporter induced dramatic 
reduction in the enzyme activity and mRNA expression of luciferase, which was 
attenuated by the site-directed mutation of the two 3'-most ARE sites. IL-1β 
increased luciferase mRNA stability in a UTR-dependent manner. Knockdown of HuR 
significantly aggravated UTR-mediated instability of luciferase and inhibited 
IL-1β-induced upregulation of RGS4 mRNA. In addition, IL-1β increased cytosolic 
translocation and RGS4 mRNA binding of HuR. These findings suggest that 3'-most 
ARE sites within RGS4 3'-UTR are essential for the instability of RGS4 mRNA and 
IL-1β promotes the stability of RGS4 mRNA through HuR.