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Abstract
Viral induction of the human beta-interferon (IFN-β) gene leads to a transient accumulation of high levels of IFN-β mRNA. Previous studies have shown that the increase in IFN-β mRNA levels after induction is due to an increase in the rate of IFN-β gene transcription. In this paper, we show that the rapid postinduction decrease in the level of IFN-β 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-β gene. Analysis of the sequence requirements for IFN-β 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.