Dissociation of basal turnover and cytokine-induced transcript stabilization of the human cyclooxygenase-2 mRNA by mutagenesis of the 3'-untranslated region

Abstract

The immediate early gene cyclooxygenase-2 (Cox-2), which encodes the inducible prostaglandin synthase enzyme, is regulated at the level of post-transcriptional mRNA turnover. In this study, the functional role of the 3'-untranslated region (3'-UTR) of the human Cox-2 gene was characterized. Deletion of the distal region of the 3'-UTR strongly inhibited basal mRNA turnover, suggesting that this region contains mRNA instability determinants. However, deletion of the proximal highly-conserved region (CR1: 6082-6198) resulted in increased basal turnover, indicating that it determines mRNA stability. All of the 3'-UTR constructs conferred IL-1-induced stabilization but not dexamethasone-induced down-regulation. Thus, distinct regions of the 3'-UTR of the Cox-2 transcript are involved in the regulation of basal and cytokine-induced mRNA metabolism.