Knight E, Anton E D, Fahey D, Friedland B K, Jonak G J
Proc Natl Acad Sci U S A. 1985 Feb;82(4):1151-4. doi: 10.1073/pnas.82.4.1151.
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.
当用人β干扰素（IFN-β）处理抑制人淋巴母细胞系Daudi细胞生长时，c-myc基因的mRNA减少超过75%。在本通讯中，我们描述了IFN-β处理对Daudi细胞c-myc基因转录以及细胞质中c-myc mRNA稳态水平的影响。结果显示，虽然从未经处理的细胞或经IFN-β处理3小时或24小时的细胞中分离的细胞核内，c-myc转录速率没有显著差异，但在IFN-β处理3小时内，细胞质中c-myc mRNA水平降低了60%。这些结果表明，IFN-β在转录后水平调节c-myc mRNA。这些结果与在相同条件下在这些细胞中于转录水平受到调节的两个IFN-β诱导基因的调节情况形成对比。我们还在经IFN-β处理的Daudi细胞中检测到了（2'-5'）寡腺苷酸合成酶（2-5A合成酶）基因的诱导。由于某些c-myc转录本有能力形成双链RNA区域，我们提出在经IFN-β处理的细胞中c-myc可在转录后水平受到调节的一种机制是，通过其自身的双链性激活2-5A合成酶/RNase L核酸内切酶系统，这会导致c-myc RNA的选择性降解。
