Abstract #48

The NatA N^a-acetyltransferase complex modulates conversion of Sup35 to the prion ([PSI⁺]) state.
Rochele R. Yamamoto, Tricia R. Serio
MCB, Brown University, 69 Brown Street, Providence, RI, 02912, USA

Sup35 is a component of the translation termination machinery whose function can be modulated epigenetically by a prion mechanism. Unlike most proteins, Sup35 is conformationally flexible, adopting a range of physical states in vivo. Each of these forms has a distinct activity level that can be transmitted to daughters. The stability of these protein-based phenotypes results from an in vivo bias in Sup35 biogenesis: newly made protein adopts the form pre-exisiting in the cell. To explore the genetic basis of this bias, we analyzed the effects of N^a-acetyltransferass on Sup35 prion propagation in vivo. When one of these complexes, the NatA N^a-acetyltransferase is disrupted in a prion background ([PSI⁺]), the cells become phenotypically non-prion ([psi^-]) but retain the ability to transmit [PSI⁺] to wildtype mating partners. The reappearance of the [PSI⁺] phenotype upon complementation of the NatA defect suggests that the efficiency rather than the pathway of conversion to the prion state has been altered. Indeed, the results of biochemical and guanidine HCl curing experiments are consistent with a model in which Sup35 accumulates in both prion and non-prion forms in mutant cells. Genetic studies indicate that N^a-acetylation of Sup35 is not required for efficient conversion to the prion form. We provide the first evidence of genetic regulation of conversion to the prion form and indicate that the presence of Sup35[PSI⁺] alone is not sufficient to induce these transitions.
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