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题目:: RNA-binding protein HuR regulates RGS4 mRNA stability in rabbit colonic smooth muscle cells.
作者:: Li(Fang),Hu(Danielle Y),Liu(Shu),Mahavadi(Sunila),Yen(William),Murthy(Karnam S),Khalili(Kamel),Hu(Wenhui)
状态:: 发布时间2010-12-01 , 更新时间 2016-10-19
期刊:: Am J Physiol Cell Physiol
摘要:: 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.
语言:: eng
DOI:

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