The yeast non-Mendelian factor [ETA+] is a variant of [PSI+], a prion-like form of release factor eRF3

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.