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s of invited paperst Regulation of gene expression by interferons We have isolated cDNAs corresponding to several different mRNAs induced by a-interferon (IFN) in human cells. Two code for metallothionein II (MT II) and a class I HLA; the others code for proteins of unknown sequence. The levels of all the mRNAs increase 5-to 40-fold about 1 day after treatment with IFN. Synthesis of new proteins is not required for induction. In IFN-resistant Daudi cells which retain IFN receptors, MT II, HLA and 2-5A synthetase mRNAs are induced normally, but several of the others are not induced. It seems likely that there are at least two pathways for induction, possibly reflecting a diversity of receptor function. In HeLa cells, most of the mRNAs are induced both by x-and y-IFNs, but at least one is preferentially induced by oa-IFN. The mRNA for c-myc decreases in response to a-IFN but increases in response to y-IFN. Thus, the control of IFN-inducible mRNAs is complex. The rate of transcription of the 1-8 mRNA, measured in nuclear runoff experiments, doubles 5 min after treatment with IFN, reaches a maximum by 60 min, and falls to the uninduced rate by 8-12 h. Activation of transcription also plays a major role in increasing the levels of MT II and HLA mRNAs in IFN-treated cells. In addition, from parallel measurements of rates of mRNA accumulation and transcription, it is clear that post-transcriptional events are also important in increasing the levels of IFN-induced mRNAs. When regions upstream of the human genes for MT II, 2 class I HLAs and one class II HLA are compared, a homologous sequence of 15 base pairs is revealed. Similar sequences have also been found near the 5' ends of IFN-induced mouse genes. The functions of these sequences are being characterised. The IFN-regulated human 6-16 gene, transfected into mouse cells, can be induced by mouse IFN. Therefore, it should be possible to conduct a detailed analysis of the promoter region. Interferon (IFN) enhances cell surface levels of HLA class I and II histo compatibility molecules as well as f2 microglobulin. This increment follows the enhancement of the corresponding messenger RNA in the cytoplasm of cells analysed. Using isolated nuclei which allows direct quantification of the transcription rate of defined genes, one could show that IFN-,B and y enhance the transcription rate of HLA class I and fl microglobulin gene in a 3-4-fold ratio after …

Joint meeting of the British & Irish Associations for Cancer Research November 28-29, 1985, London. Abstracts