An evaluation of messenger RNA competition in the shutoff of human interferon production.

Abstract

The process that shuts off poly(I).cntdot.poly(C)-induced interferon production in a strain of diploid human fibroblasts (FS-4) involves the synthesis of new RNA, presumably nuclear heterogeneous RNA. When cultures in the shutoff phase of interferon production are treated with actinomycin D (5 .mu.g/ml) or 5,6-dichloro-1-.beta.-D-ribofuranosylbenzimidazole (DRB, 40 .mu.M), the rate of interferon production continues to decline for a further 3-4 h, but then tends to level off. The treated cultures maintain interferon production at a reduced level for at least 10 h. The residual rate of interferon production is higher in cultures which received actinomycin D or DRB early in the shutoff phse as compared to the rate in cultures treated late. Actinomycin D and DRB reduced the overall rate of cellular RNA synthesis by > 98% and 60%, respectively. These kinetic data are incompatible with the possibility that the shutoff of interferon production is due to simple competition by newly synthesized mRNA. These data are consistent with the post-transcriptional repressor hypothesis, and suggest that the putative repressor system that shuts off interferon production has a life-time of 3-4 h at 37.degree. C and that its effect on the synthesis of interferon is largely irreversible.