Abstract

The yeast non-Mendelian factor [ETA⁺] is lethal in the presence of certain mutations in the SUP35 and SUP45 genes, which code for the translational release factors eRF3 and eRF1, respectively. One such mutation, sup35-2, is now shown to contain a UAG stop codon prior to the essential region of the gene. The non-Mendelian inheritance of [ETA⁺] is reminiscent of the yeast [PSI⁺] element, which is due to a self-propagating conformation of Sup35p. Here we show that [ETA⁺] and [PSI⁺] share many characteristics. Indeed, like [PSI⁺], the maintenance of [ETA⁺] requires the N-terminal region of Sup35p and depends on an appropriate level of the chaperone protein Hsp104. Moreover, [ETA⁺] can be induced de novo by excess Sup35p, and [ETA⁺] cells have a weak nonsense suppressor phenotype characteristic of weak [PSI⁺]. We conclude that [ETA⁺] is actually a weak, unstable variant of [PSI⁺]. We find that although some Sup35p aggregates in [ETA⁺] cells, more Sup35p remains soluble in [ETA⁺] cells than in isogenic strong [PSI⁺] cells. Our data suggest that the amount of soluble Sup35p determines the strength of translational nonsense suppression associated with different [PSI⁺] variants.