Alpha-interferon inhibits the expression of heavy chain mu messenger RNA in Daudi cells.
A clone of Daudi cells (Daudi-S) synthesizes the heavy chain of IgM (mu-chain) under routine conditions of cell culture. In the presence of alpha-interferon, however, synthesis of mu-chain is decreased rapidly at a time when the overall protein synthesis is not modified and the dsRNA-dependent protein kinase and the 2-5A synthetase are induced. This inhibition of mu-chain synthesis seems to be correlated with the antiproliferative action of interferon since it occurs only slightly in another clone of Daudi cells resistant (Daudi-R) to the antiproliferative action of interferon. In these resistant cells, however, the protein kinase and the 2-5A synthetase are induced by interferon. Specific inhibition of mu-chain synthesis in interferon-treated Daudi-S cells is a consequence of decreased steady-state levels of mu-chain mRNA. This effect occurs 4-8 h after addition of interferon in parallel with decreased levels of c-myc mRNA and enhanced levels of HLA mRNA. Reduced levels of mu-chain mRNA in interferon-treated Daudi-S cells is not a consequence of its enhanced degradation as shown by actinomycin D chase experiments. Furthermore, nuclear run on experiments rule out an effect on the transcription of mu-chain mRNA. Therefore, the inhibitory mechanism mediated by interferon might be at the level of termination and/or post-transcriptional processing of mu-chain RNA. In contrast, in these same interferon-treated Daudi-S cells, the inhibition of c-myc gene expression is due to an enhanced degradation of its mRNA (in accord with other reports). These data indicate that interferon can inhibit gene expression by different mechanisms.
D000911:Antibodies, Monoclonal / Q000276:immunology; D002051:Burkitt Lymphoma / Q000473:pathology*; D002455:Cell Division; D005786:Gene Expression Regulation / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics*; D007370:Interferon Type I / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D007370:Interferon Type I; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell