An antisense interferon-beta RNA abolishes repression of c-fos gene expression.
To determine the cellular functions which are modified when interferon-beta (IFN-beta) gene expression is inhibited, a plasmid allowing the constitutive expression of RNA complementary to IFN-beta mRNA was constructed and stably introduced into L929 cells. Some of the selected clones expressing this antisense IFN-beta mRNA, named L-ASI, were unable to produce IFN-beta and lost the ability to arrest in the G0 phase of the cell cycle. Indeed, the usual transrepression of the c-fos gene observed in quiescent cells was blocked in IFN-beta antisense L-ASI clones and the c-fos gene was permanently stimulated. This overexpression of c-fos was not modified in response to protein kinase C agonists such as phorbol esters, but increased in response to the adenylate cyclase activator forskolin. In addition, the ability to induce major histocompatibility class I genes following recombinant IFN-beta treatment was impaired in antisense IFN-beta L-ASI clones, suggesting an important alteration of this cell with regard to the interferon system. Unexpectedly, the tumorigenicity of the clones was significantly diminished. We postulate that IFN-beta antisense RNA blocks the repression of the c-fos gene and thus prevents the arrest of cells in the G0 phase of the cycle.
Lallemand
C
C
Unité 153 INSERM, Paris, France.
Kahan
A
A
Telvi
L
L
Joret
A M
AM
Gerfaux
J
J
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002467:Cell Nucleus / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D005576:Colforsin / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D016762:Genes, fos / Q000187:drug effects; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics*; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D009522:Newcastle disease virus / Q000276:immunology; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D016133:Polymerase Chain Reaction; D016372:RNA, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D015183:Restriction Mapping; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D016372:RNA, Antisense; D012333:RNA, Messenger; D005576:Colforsin; D016899:Interferon-beta; D004247:DNA