Interferon regulates c-myc gene expression in Daudi cells at the post-transcriptional level.
c-myc gene mRNA is reduced by greater than 75% in the human lymphoblastoid cell line Daudi when growth is inhibited by treatment with human interferon beta (IFN-beta). In the present communication, we describe 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. The results 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-beta for 3 or 24 hr, the level of c-myc mRNA in the cytoplasm is reduced by 60% within 3 hr of IFN-beta treatment. These results suggest that IFN-beta regulates the c-myc mRNA at a post-transcriptional level. These results are in contrast to the regulation of two IFN-beta-induced genes that under identical conditions are regulated in these cells at the transcriptional level. We have also detected induction of the (2'-5')oligoadenylate synthetase (2-5A synthetase) gene in IFN-beta-treated Daudi cells. Since certain c-myc transcripts have the capacity to form double-stranded RNA regions, we propose that one 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.
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D009857:Oncogenes / Q000187:drug effects*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism
D007370:Interferon Type I; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015088:2',5'-Oligoadenylate Synthetase