Heterologous gln/asn-rich proteins impede the propagation of yeast prions by altering chaperone availability

Abstract

The infectivity of transmissible spongiform encephalopathies (TSEs) was explained by the prion hypothesis proposing that the inheritance of biological information can be achieved by self-propagating conformational changes in the prion protein PrP [1]. The prion list has since been extended to include protein-based genetic elements found in fungi [2]. The beststudied yeast prions [PSI+], [PIN+] (often called [RNQ+]) and [URE3] are, respectively, self-propagating conformations of: Sup35, a translation termination factor; Rnq1, a protein of unknown function; and Ure2, a nitrogen catabolism repression regulator [3]-[5]. Other recently discovered yeast prions include [SWI+], [OCT+], [ISP+], [MOT3+] and [MOD5] [6], [7]. The propagation of most [8]-[10], but not all [6] yeast prions is driven by their Q/N-rich prion domains that have the propensity to form aggregates in vivo and assemble into self-seeding, β-sheet-rich amyloid fibers in vitro 11,12.