mRNA stability influences the temporal order of inflammatory gene induction

The inflammatory response plays out over time in a reproducible and organized manner after an initiating stimulus. Here we showed that the genes activated in cultured mouse fibroblasts in response to the proinflammatory cytokine tumor necrosis factor can be divided roughly into three groups, each with different induction kinetics. Whereas differential transcription is important in determining the grouping of these genes, differential mRNA stability also exerted strong influence in some cases overriding that of transcriptional control elements on the temporal order of gene expression. mRNA transcripts expressed early after TNF stimulation have abundant AU-rich elements in their 3'-untranslated regions whereas those expressed later are contain fewer AU-rich sequences. Thus mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of proinflammatory cytokine-induced gene expression. The gene expression levels were monitored in the mouse embryonic cells stimulated with TNF for 0, 0.5h, 2h and 12 hours.