Interferon regulates c-myc gene expression in Daudi cells at the post-transcriptional level.

Abstract

C-myc gene mRNA is reduced by > 75% in the human lymphoblastoid cell line Daudi when growth is inhibited by treatment with human interferon .beta. (IFN-.beta.). The effect of IFN-.beta. treatment on transcription of the c-myc gene and on the steady-state level of c-myc mRNA in the cytoplasm of Daudi cells is described. Although the rate of c-myc transcription is not significantly different in nuclei isolated either from untreated cells or from those treated with IFN-.beta. for 3 or 24 h, the level of c-myc mRNA in the cytoplasm is reduced by 60% within 3 h of IFN-.beta. treatment. IFN-.beta. may regulate the c-myc mRNA at a post-transcriptional level. These results are in contrast to the regulation of 2 IFN-.beta.-induced genes that under identical conditions are regulated in these cells at the transcriptional level. Induction of the (2''-5'')oligoadenylate synthetase (2-5A synthetase) gene was detected in IFN-.beta.-treated Daudi cells. Since certain c-myc transcripts have the capacity to form double-stranded RNA regions, 1 mechanism by which c-myc could be regulated post-transcriptionally in IFN-.beta.-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.