A bipolar personality of yeast prion proteins

Abstract

Prions are infectious, self-propagating protein conformations. [PSI+], [RNQ+] and [URE3] are well characterized prions in Saccharomyces cerevisiae and represent the aggregated states of the translation termination factor Sup35, a functionally unknown protein Rnq1, and a regulator of nitrogen metabolism Ure2, respectively. Overproduction of Sup35 induces the de novo appearance of the [PSI+] prion in [RNQ+] or [URE3] strain, but not in non-prion strain. However, [RNQ+] and [URE3] prions themselves, as well as overexpression of a mutant Rnq1 protein, Rnq1Δ100, and Lsm4, hamper the maintenance of [PSI+]. These findings point to a bipolar activity of [RNQ+], [URE3], Rnq1Δ100, and Lsm4, and probably other yeast prion proteins as well, for the fate of [PSI+] prion. Possible mechanisms underlying the apparent bipolar activity of yeast prions will be discussed.

Figure 1

A possible mechanism for the inhibition of the maintenance of [PSI⁺] prion by overproduced Pin⁺ proteins. Under normal situations, Hsp104 breaks up [PSI⁺] amyloid filaments to generate prion seeds for efficient prion transmission. Under Pin⁺ overproduction conditions, Pin⁺ proteins accelerates a size enlargement of [PSI⁺] amyloid fibrils through tip-to-tip or side-by-side interactions, giving rise to overgrown [PSI⁺] amyloids that are incapable of reaching daughter cell.