Intron 1 mediated regulation of bovine prion protein gene expression: Role of donor splicing sites, sequences with potential enhancer and suppressor activities.
Prion protein plays a key role in the pathogenesis of transmissible spongiform encephalopathies. Because changes in expression of the prion protein gene (PRNP) alter the incubation time and severity of prion diseases. Our previous work revealed a strong association between the promoter (spanning base pairs (bp) -88 to -30) and intron 1 (spanning bp +114 to +892) that leads to optimum expression of the bovine PRNP. Here, we employed two mutation analysis strategies (deletion and insertion) and two reporter assay systems (luciferase and GFP expression) to define the regulatory domains within intron 1 and further elucidate its role in regulating the promoter activity of the bovine prion protein gene. We identified DNA sequences with potential suppressor and enhancer activities within the 5' end of intron 1. Moreover stability analyses for PRNP mRNAs demonstrated that splicing sites and mechanism are critical for bovine PRNP expression.
Elmonir
Walid
W
Laboratory of Food and Environmental Hygiene, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, Gifu 501-1193, Japan.
Inoshima
Yasuo
Y
Elbassiouny
Ahmed
A
Ishiguro
Naotaka
N
D000818:Animals; D001483:Base Sequence; D002417:Cattle / Q000235:genetics*; D002460:Cell Line; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D054643:INDEL Mutation; D007438:Introns; D011328:Prions / Q000235:genetics*; D022821:RNA Splice Sites; D015533:Transcriptional Activation
D011328:Prions; D022821:RNA Splice Sites