IFN-γ inhibits c-myc gene expression by impairing the splicing process in a colony-stimulating factor dependent murine myeloid cell line

Proliferation of NSF-60.8 cells, a CSF-dependent murine myeloid cell line, is strongly inhibited by murine IFN-γ. Northern analysis of growth arrested, NSF-60.8 cells activated by addition of CSF in the presence or absence of IFN-γ indicated that IFN-γ inhibited the induction of c-myc mRNA steady state level by CSF. The effect was observed as early as 30 min after induction and the inhibition was complete after 20 h. IFN-γ did not impair the transcriptional activation of c-myc gene, and it had only a slight destabilizing effect on the mature c-myc message. Study of the processing steps of c-myc mRNA precursor indicated that in the presence of IFN-γ, a putative 3.6-kb splice intermediate accumulated instead of the mature message, suggesting that IFN-γ inhibits the splicing of c-myc precursor.