Award details

The 5'-leader sequence of PrP mRNA

Reference	BBS/E/I/00000643
Principal Investigator / Supervisor	Professor Nora Hunter
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	48,592
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	30/03/2000
Duration	35 months

Abstract

The PrP gene of ruminants contains at least three exons, two of which contribute to the short, untranslated 5' leader sequence of PrP mRNA. This arrangement is also found in rodent PrP but not yet in human PrP. The specific function of this sequence is not known, one possibility being control of spatial and/or tissue specific expression in the brain. Recently it has been shown for the hamster gene that alternative splicing to the 5' leader sequence exists and differential expression is linked to the resulting mRNA species. There is also evidence from the bovine and mouse PrP gene for the existence of a second promoter which may lead to a different leader sequence. Thirdly, it has been reported that the exon I sequence in bovine PrP RNA varies in length. Finally, the conservation of parts of the 5' leader even when compared to chicken PrLP mRNA is very high and little polymorphic variation has been observed so far, suggesting an important and maybe evolutionary conserved function. This is, for example, in marked contrast to the high frequency of polymorphisms and interspecies variation in the 3' untranslated region of PrP mRNAs, Untranslated regions of mRNAs can play a major role in the translatability and stability of RNA modulating therefore the temporal and spatial kinetics of the expression of the encoded protein. We have already evidence for translational regulation through the 3' region. We propose to extend our preliminary experiments on the 5' leader sequence of sheep mRNA to investigate potential variation in sequence and function of this region. RNA from different brain areas will be analysed for different 5' leader sequences by 5' RACE and Northern blot analysis. Cells will be transfected with reporter gene constructs containing different variants of 5' leaders. The similarity of sheep, goat and cattle gene (cDNA/mRNA) in this region will be analysed.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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