Tumor necrosis factor-alpha regulation of glucose transporter (GLUT1) mRNA turnover. Contribution of the 3'-untranslated region of the GLUT1 message.
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.
McGowan
K M
KM
Department of Biochemistry, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA.
Police
S
S
Winslow
J B
JB
Pekala
P H
PH
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D004591:Electrophoresis, Polyacrylamide Gel; D051272:Glucose Transporter Type 1; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D017384:Sequence Deletion; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; D014409:Tumor Necrosis Factor-alpha