Regulation of GLUT4 mRNA stability by tumor necrosis factor-alpha: alterations in both protein binding to the 3' untranslated region and initiation of translation.

Previous studies from our laboratory have demonstrated that exposure of the 3T3-L1 adipocytes to TNF resulted in a 50% decrease in the half-life of the GLUT4 mRNA from 9.5h (control) to 4.5h (treated cells). In the current study we report that coincident with the alteration of the half-life of the message, TNF treatment resulted in an increase in the binding of a protein to the proximal 200 bases of the 3'UTR. In addition the distribution of GLUT4 mRNA in polysome profiles was altered such that message accumulated as a 40S preinitiation complex, consistent with an attenuation of initiation. In summary, our data suggest that enhanced decay of the GLUT4 mRNA may occur through a mechanism involving accumulation of a 40s preinitiation complex which correlates with increased protein binding to the 3'UTR.