Interferon regulates c-myc gene ex post-transcriptional level (blot hybridization/cell growth inhibition/in vitro nuclear transcriptii

c-myc gene mRNA is reduced by >75% in the human lymphoblastoid cell line Daudi when growth is in- hibited by treatment with human interferon B (IFN-/f). In the present communication, we describe the effect of IFN-3 treat- ment on transcription of the c-myc gene and on the steady-state level of c-myc mRNA in the cytoplasm of Daudi cells. The re- sults show that, although the rate of c-myc transcription is not significantly different in nuclei isolated either from untreated cells or from those treated with IFN-P for 3 or 24 hr, the level of c-myc mRNA in the cytoplasm is reduced by 60% within 3 hr of IFN-P treatment. These results suggest that IFN-/ regu- lates the c-myc mRNA at a post-transcriptional level. These results are in contrast to the regulation of two IFN-jl-induced genes that under identical conditions are regulated in these cells at the transcriptional level. We have also detected induc- tion of the (2'-5')oligoadenylate synthetase (2-5A synthetase) gene in IFN-,B-treated Daudi cells. Since certain c-myc tran- scripts have the capacity to form double-stranded RNA re- gions, we propose that one mechanism by which c-myc could be regulated post-transcriptionally in IFN-/3-treated cells is by activating, through its own double-strandedness, the 2-5A synthetase/RNase L endonuclease system, which would cause selective degradation of the c-myc RNA.