Upstream AUGs modulate prion protein translation in vitro

The level of expression of the host PrP gene (PRNP) has been shown to affect the progression to a disease, transmissible spongiform encephalopathy (TSE). In order to define sequences that are responsible for translation ofPRNPmRNA we have investigated a region comprising its 5'-leader sequence. Most remarkable, it consists of an almost identical Kozak mRNA sequence and two AUG initiation codons which seem to modulate translation of the prion protein mRNA in vitro. Although transcriptional regulation of the prion protein PRNP gene had been expected to dominate the translational modulation, our observations point to a translational regulation of the mouse prion protein synthesis controlled by ribosomal entry and usage of AUG codons.