Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene

Abstract

PrP 27-30 is the major protein in purified preparations of scrapie agent. An almost complete PrP cDNA was used to select PrP-related genomic clones from normal hamster DNA. The gene contains a noncoding exon of 56 to 82 bp and a 2 kb coding exon, separated by a 10 kb intron. Transcription initiates at the same multiple sites in vivo and in vitro. The promoter lacks a TATA box and contains three repeats of the sequence GCCCCGCCC, which resembles the Sp1 binding site found in "housekeeping" genes. The PrP coding sequence encodes a presumptive amino-terminal signal peptide. The primary structure of PrP encoded by the gene of a healthy animal does not differ from that encoded by a cDNA from a scrapie-infected animal, suggesting that the different properties of PrP from normal and scrapie-infected brains are due to post-translational events.

Molecular biology of transmissible spongiform encephalopathies

“…PrP c is a normal host protein [14][15][16] found predominantly on the outer surface of neurons ( Fig. 1).…”

“…The entire PrP coding sequence is contained within one exon of the singular Prnp gene [16]. As shown in Fig.…”

“…Seed formation is kinetically controlled and extremely slow; once a seed is present, monomer addition can ensue at a rapid rate [58,59]. [16,21,29]. Pulse-chase experiments in scrapie-infected neuroblastoma cells suggest that PrP c is converted to PrP sc either at the cell surface or following endocytosis [30].…”

Nucleotide sequence of the Drosophila glucose-6-phosphate dehydrogenase gene and comparison with the homologous human gene

“…Although most genes containing PolII promoters possess a 'TATA' box, there are PolII promoters that lack the TATA box (Nevins, 1983). In particular, many housekeeping genes, i.e., genes which are fairly uniformly expressed in most tissue types throughout the life cycle of the organism, do not possess a TATA box: the hydroxymethyl glutaryl CoA reductase gene (Reynolds et al, 1984), the hypoxanthine phosphoribosyltransferase gene (Pate1 et al, 1986;Melton et al, 1984), the adenosine deaminase gene (Valerio, 1985), the DHFR gene (Masters and Attardi, 1985;Mitchell et al, 1986), one of the two glyceraldehyde-3-phosphate dehydrogenase genes in Drosophila (Tso et al, 1985) as well as the PrP 27-30 gene (Basler et al, 1986) and the Ul RNA gene (Roebuck and Stump, 1985). These genes do, however, contain one or more copies of the sequence GGGCGG or its inverse complement CCGCCC upstream from their transcription start point.…”

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

“…In humans, PRNP is located on chromosome 20 and comprises two exons (Basler et al, 1986). Transcription of the second exon gives rise to the complete PrP c protein (Puckett et al, 1991).…”