Abstract
9-27 mRNA is expressed to a high level in response to both alpha and gamma interferons. In contrast, 6-16 mRNA is expressed well in response to alpha but very poorly in response to gamma interferon in human cells. The factors governing these different levels of expression were investigated. For both genes the major effect of both interferons is on transcription. A transcriptional bias in the 6-16 promoter/enhancer accounts in large part for the differential response of 6-16 to the two interferons. No single DNA element appears responsible; the smaller the 5' region analysed the lower the absolute activity and the smaller the differential response to alpha and gamma interferons observed. Both the 6-16 and 9-27 mRNAs are very stable and no effect of the interferons on stability was detected. Nor was any direct evidence obtained for preferential processing of the 9-27 mRNA. Nevertheless, differentials between the transcription and accumulation of mature mRNAs, particularly for 6-16 mRNA in response to gamma interferon, suggest that post-transcriptional control(s) must additionally operate. The 9-27 5' promoter/enhancer is much less active than that from 6-16 when placed 5' of a marker gene, despite the similar response of the two genes to alpha interferon.
MeSH Terms
Blotting, Northern
Cells, Cultured
DNA Mutational Analysis
Enhancer Elements, Genetic
Gene Expression Regulation
Genes
Humans
Interferon Type I/pharmacology
Interferon-gamma/pharmacology
Metabolic Clearance Rate
Multigene Family/genetics
Promoter Regions, Genetic
RNA Processing, Post-Transcriptional
RNA, Messenger/genetics,metabolism
Recombinant Proteins
Transcription, Genetic/drug effects
Chemicals
Interferon Type I
RNA, Messenger
Recombinant Proteins
Interferon-gamma
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Ackrill A M
Imperial Cancer Research Fund, London, UK.
Reid L E
Gilbert C S
Gewert D R
Porter A C
Lewin A R
Stark G R
Kerr I M
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