FIGURE 2.

Model of promoter-mediated activation of transcription of COX-2. (A) In the basal state, promoter RNAs are expressed at the COX-2 promoter in the sense direction. COX-2 and PLA2G4A are expressed at low levels. The sense promoter RNA is a platform for recognition by a small complementary RNA (endogenous or synthetic) and recruitment of AGO2 and TNRC6. For gene activation, binding of a small RNA in complex with AGO2 and TNRC6 leads to association of transcription factors and WDR5 and an increase in activating histone marks. Gene looping that juxtaposes the COX-2 and PLA2G4A promoters enables activation of both genes. (B) Summary of some of the key mechanistic findings from RNA-mediated COX-2 activation.