Tumor Necrosis Factor-α Regulation of Glucose Transporter (GLUT1) mRNA Turnover

Abstract

In the current study we report on the contribution of the GLUT1 3'-untranslated region (UTR) to the stability of the GLUT1 mRNA. To facilitate these investigations, a hybrid construct was prepared by insertion of the GLUT1 3'-UTR into a normally stable reporter gene coding for preproinsulin. The GLUT1 3'-UTR conferred lability to the otherwise long lived construct and transferred an ability to be stabilized in response to treatment with the cytokine, tumor necrosis factor-alpha (TNF). The destabilizing element has been mapped to a region located between bases 2242 and 2347 of the GLUT1 3'-UTR; this same region also mediates the stabilization response to TNF. In vitro RNA-protein binding assays using protein extracts from control and TNF-treated cells demonstrated that two proteins, one of 37 kDa and the other of 40 kDa, recognized sequence elements within the stability-determining region and were up-regulated in response to TNF treatment. The RNA-binding activity of these proteins coincides with the stabilization of the GLUT1 message, suggesting that they may be involved in regulation of the turnover of this message.