Regulation of prion protein expression by noncoding regions of the Prnp gene.

Expression of the cellular prion protein is necessary for the transmission and propagation of prion diseases. Increasing the level of prion protein expression decreases the incubation period for these diseases. Therefore, understanding the regulation of prion protein expression could be critical for treating or preventing these diseases. We investigated the regulation of prion protein expression by the promoter and noncoding regions of the bovine and murine Prnp genes. We determined that expression is modulated by intron 1 and exon 1. In the absence of intron1, exon 1 inhibited activity of the promoter. However, intron 1 demonstrated promoter-like activity and possessed a TATA box. In addition, we identified an alternative transcript present in the brains of cattle and mice that lacks exon 1. Taken together, these results show that intron 1 and exon 1 play a critical role in the regulation of prion protein expression. Because switching off prion protein expression has been shown to arrest prion disease, these regions present novel targets for intervention in the disease process.