REGULATION OF GLUT4 MESSENGER-RNA 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 o f 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) (1) . In the current study we report that coincident with the alteration o f 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 alte red such that message accumulated as a 40S preinitiation complex, cons istent with an attenuation of initiation. In summary, our data suggest that enhanced decay of the GLUT4 mRNA may occur through a mechanism i nvolving accumulation of a 40s preinitiation complex which correlates with increased protein binding to the 3'UTR. (C) 1996 Academic Press, Inc.