The 3 '-untranslated region of murine cyclooxygenase-2 contains multiple regulatory elements that alter message stability and translational efficiency

Renal mesangial cells regulate their expression of the pro-inflammatory gen e cyclooxygenase-2 (COX-2) through mechanisms involving gene transcription and post-transcriptional events. Post-transcriptional regulation of COX-2 i s dependent, in part, on sequences within the 3'-untranslated region (3'-UT R) of the COX-2 mRNA Insertion of the entire 3'-UTR of COX-2 into the 3'-UT R of luciferase resulted in a 70% decrease in luciferase enzymatic activity . Measurement of steady-state reporter gene mRNA levels suggested that the loss of activity was due to decreased translational efficiency. Deletion an alysis identified the first 60 nucleotides of the 3'-UTR of COX-2 as a majo r translational control element. This region of the 3'-UTR of COX-2 is high ly conserved across species; is AU-rich; and contains multiple repeats of t he regulatory sequence AUUUA, reported to confer post-transcriptional contr ol. In addition, we identified regions of the 3'-UTR of COX-2 outside of th e first 60 nucleotides that altered message stability. Some of these region s contained AUUUA consensus sequences, whereas others did not, and represen t novel control elements. These results suggest that expression of COX-2 in mesangial cells depends on the complex integration of multiple signals der ived from the 3'-UTR of the message.