Inactivation of interferon mRNA in the shutoff of human interferon synthesis.

Abstract

INDUCTION of interferon synthesis in cultured cells by rIn.rCn has been intensely studied because of its attractiveness as a model for gene expression in mammalian cells and its possible significance to medicine. Exposure of human fibroblast FS-4 cells to rlu.rCn results in interferon (IF) synthesis which persists for 6 h and then abruptly shuts off1,2. The rapidity of this shutoff indicates that the cessation of IF mRNA transcription is unlikely to be the primary control. Moreover, studies with metabolic inhibitors3–7 have suggested that a post-transcriptional event is involved. To evaluate the role of post-transcriptional control in the shut-off of IF production, we measured directly the level of IF mRNA activity in a strain of human fibroblast HF 926 cells during the IF induction process. This was achieved by the development of a highly efficient and reproducible heterologous whole cell transnational system. We report here that, using this system, we have found a significant decrease in the IF mRNA activity during the shutoff of IF protein synthesis.