PrP (prion) gene expression in sheep may be modulated by alternative polyadenylation of its messenger RNA

Abstract

Scrapie-associated fibrils and their major protein component, PrP or prion protein, accumulate in the brains and some other tissues of all species affected by transmissible spongiform encephalopathies or prion diseases. To investigate the role of PrP gene expression in the hosts of these diseases, we have analysed some characteristics of PrP gene RNA transcripts in sheep and cattle tissues and made comparisons with PrP RNA transcripts in human and mouse tissues. Two PrP messenger RNAs of 4·6 kb and 2·1 kb, the result of alternative polyadenylation, were found first in sheep peripheral tissues and also occurred at low levels in sheep brain and bovine tissues, but not in human and mouse tissues. Our results from transfection assays of murine neuroblastoma cells with constructs expressing different regions of ovine PrP messenger RNA revealed the presence of sequences in the 3′ untranslated region of the gene that modulate protein synthesis.