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

The yeast non-Mendelian factor [ETA(+)] is lethal in the presence of certai n mutations in the SUP35 and SUP35 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 yeas t [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 ne 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 Sup 35p 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+] var iants.