Induced frameshifting mechanism of replication for an information-carrying scrapie prion

Microbial Pathogenesis
P R Wills

Abstract

A specific mistranslation mechanism for the replication of an infectious protein is described. The feedback mechanism requires the infectious agent to induce concerted frameshifts during the translation of a cellular gene. Each module of the tandem repeat region of the gene encoding the prion protein (PrP) associated with scrapie infectivity contains multiple sites of potential ribosomal frameshifting. It is proposed that some aberrant variants of PrP containing frameshifted peptides within the octapeptide repeat region of the protein backbone are able to replicate and cause scrapie by interfering with the translation and simultaneous translocation of nascent PrP molecules into the lumen of the endoplasmic reticulum. The model provides a plausible explanation for the behaviour of host-adapted scrapie strains as well as the aetiology of scrapie-like diseases. The hypothesis that a mistranslated PrP is the scrapie agent can also explain discrepancies between the published amino acid sequence of PrP and the sequence deduced from the gene.

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Citations

Dec 11, 1991·Proceedings of the National Academy of Sciences of the United States of America·L G GoldfarbD C Gajdusek
Jun 1, 1991·New Zealand Veterinary Journal·P R Wills
Mar 5, 2013·Journal of Theoretical Biology·Peter R Wills
Aug 22, 1991·Nature·C Weissmann
Aug 2, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Peter R Wills
Oct 1, 1994·Animal Genetics·H L NeibergsJ L Williams

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