Postinduction turnoff of beta-interferon gene expression.
Viral induction of the human beta-interferon (IFN-beta) gene leads to a transient accumulation of high levels of IFN-beta mRNA. Previous studies have shown that the increase in IFN-beta mRNA levels after induction is due to an increase in the rate of IFN-beta gene transcription. In this paper, we show that the rapid postinduction decrease in the level of IFN-beta mRNA is due to a combination of transcriptional repression and rapid turnover of the mRNA. This transcriptional repression can be blocked with cycloheximide, suggesting that the synthesis of a virus-inducible repressor is necessary for the postinduction turnoff of the IFN-beta gene. Analysis of the sequence requirements for IFN-beta mRNA instability revealed two regions capable of destabilizing a heterologous mRNA. One destabilizer is an AU-rich sequence in the 3' untranslated region, and the other is located 5' to the translation stop codon.
Whittemore
L A
LA
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Maniatis
T
T
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation; D007370:Interferon Type I / Q000235:genetics*; D008969:Molecular Sequence Data; D010222:Parainfluenza Virus 1, Human / Q000235:genetics*; D010957:Plasmids; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D007370:Interferon Type I; D012333:RNA, Messenger; D003513:Cycloheximide; D011070:Poly I-C