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.
Long
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Department of Biochemistry, School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
Pekala
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D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects*; D051275:Glucose Transporter Type 4; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis*; D009124:Muscle Proteins; D016296:Mutagenesis; D010442:Peptide Chain Initiation, Translational; D016133:Polymerase Chain Reaction; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D017384:Sequence Deletion; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D017931:DNA Primers; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D014409:Tumor Necrosis Factor-alpha