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Volume 272, Number 2, Issue of January 10, 1997 pp. 1331-1337
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Tumor Necrosis Factor- Regulation of Glucose Transporter (GLUT1) mRNA Turnover
CONTRIBUTION OF THE 3-UNTRANSLATED REGION OF THE GLUT1 MESSAGE

(Received for publication, May 24, 1996, and in revised form, September 20, 1996)

From the Department of Biochemistry, East Carolina University School of Medicine, Greenville, North Carolina 27858

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- (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.

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