The regulation of glucose transporter (GLUT1) expression by the RNA binding protein HuR

HuR is a ligand for nuclear mRNAs containing adenylate-uridylate-rich (ARE) elements in the 3'-untranslated region. Once bound to the mRNA, HuR is recognized by adapter proteins that then facilitate nuclear export of the complex. In the cytosol, HuR is thought to function to control stability and translation of its ligand message. We have previously demonstrated that HuR is constitutively expressed in the 3T3-L1 cells and shuttles from the nucleus to the cytosol, but remains predominantly nuclear in the preadipocytes and that as the cells differentiate, there is a marked increase in the proportion of HuR in the cytosol at any time. The GLUT1 glucose transporter is also expressed in both preadipocytes and adipocytes and in vitro RNA gel shifts indicate the mRNA is a ligand for HuR. However, HuR complexes containing the GLUT1 mRNA can only be isolated from the terminally differentiated adipocytes. Moreover, position analysis of the GLUT1 mRNA and HuR protein in polysome profiles demonstrates a shift to the most dense region of the gradient for both message and protein with adipocyte differentiation. Consistent with a regulatory role in the control of GLUT1 expression, siRNA-mediated decrease in HuR protein resulted in a decreased expression of GLUT1 protein. These data suggest that HuR contributes to the metabolic function of the adipocyte through mediation of post-transcriptional regulatory events.