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RNA-binding protein HuR regulates RGS4 mRNA stability in rabbit colonic smooth muscle cells.


ABSTRACT: 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-1?-induced upregulation of RGS4 expression. We show that IL-1? 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-1? increased luciferase mRNA stability in a UTR-dependent manner. Knockdown of HuR significantly aggravated UTR-mediated instability of luciferase and inhibited IL-1?-induced upregulation of RGS4 mRNA. In addition, IL-1? 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-1? promotes the stability of RGS4 mRNA through HuR.

SUBMITTER: Li F 

PROVIDER: S-EPMC3006324 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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RNA-binding protein HuR regulates RGS4 mRNA stability in rabbit colonic smooth muscle cells.

Li Fang F   Hu Danielle Y DY   Liu Shu S   Mahavadi Sunila S   Yen William W   Murthy Karnam S KS   Khalili Kamel K   Hu Wenhui W  

American journal of physiology. Cell physiology 20100929 6


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  ...[more]

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