65-KDA PROTEIN BINDS TO DESTABILIZING SEQUENCES IN THE IFN-BETA MESSENGER-RNA CODING AND 3' UTR

The transient expression of human interferon (IFN-beta) gene in respon se to viral induction is regulated both at the transcriptional and pos ttranscriptional levels. The decrease in levels of IFN-beta mRNA, whic h requires protein synthesis, is due to transcriptional repression as well as a rapid turnover of beta mRNA. Previous studies have shown the presence of two destabilizing sequences, one in the 3' untranslated r egion (UTR) and the other in the coding region. We have shown in this study that the coding region destabilizing element resides in the 3' e nd of the coding region (+538 to +637) and that the degradation does n ot require the translation of IFN-beta mRNA through its coding region. In addition, we have identified three domains of 19, 20, and 29 nucle otides long that specifically bind a 65-kilodalton (kDa) cytoplasmic p rotein. One of the binding sites is in the 3' end of the coding region and the other two in the 3' UTR. All these regions are AU-rich and sh ow considerable homology to each other. Interestingly, the levels of t he 65-kDa protein was increased after poly rI.rC induction. We suggest that this 65-kDa protein is a component of the IFN-beta mRNA destabil izing complex or plays a role in the degradation of IFN-beta mRNA.