Prions: proteins as genes and infectious entities

Infectious proteins (prions) include the transmissible spongiform encephalopathies (TSEs) of mammals, the amyloidoses [URE3], [PSI], and [PIN] of Saccharomyces cerevisiae and [Het-s] of the filamentous fungus Podospora anserina, and the self-activating in trans vacuolar protease B of yeast, called [β]. [Het-s] and [β] carry out cellular functions, namely, heterokaryon incompatibility and protein degradation, whereas the TSEs, [URE3], and apparently [PSI] are diseases. [PIN] appears to be neutral. We review the means of discovering prions, the interactions of these “autonomous” entities with their hosts (particularly chaperones), and the relation of prions to other nonnucleic acid heritable traits. That most amyloidoses are not infectious poses a conundrum.

We use the term “prion” (Prusiner 1982) to mean “infectious protein” in any organism, whatever the mechanism, and to imply the absence of a nucleic acid necessary for the infectivity. Although the word “prion” began its life as simply another name for the causative agent of the mammalian transmissible spongiform encephalopathies (TSEs), its usage changed with the discovery of the yeast infectious proteins [URE3] and [PSI] (Wickner 1994). These and the more recently discovered prions, [Het-s] of Podospora anserina (Coustou et al. 1997) and [PIN⁺] of yeast (Derkatch et al. 2001), are all based on self-propagating amyloid forms of chromosomally encoded proteins. The latest prion, [β] of Saccharomyces, is simply the active form of the vacuolar protease B, an enzyme that in certain conditions can be required in trans for activation of its own precursor protein (Roberts and Wickner 2003). In contrast to other prions, [β] is not a self-propagating amyloid. Other reviews also deal with a selection of these subjects (Wickner 1997; Kushnirov and Ter-Avanesyan 1998; Caughey 2000; Uptain and Lindquist 2002; Chesebro 2003; Tuite and Cox 2003; Wickner et al. 2004).

Transmissible spongiform encephalopathies

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