Year: 2025
Type: article
Abstract: It was reported that yeast proteins Ssz1 and Upf1 can cure certain [ PSI + ] variants in wild-type cells and there is a special class of variants whose propagation requires the triple mutation of ssz1 ∆ upf1 ∆ Hsp104 T160M . Attempts to isolate variants with the exact properties from the 74-D694 strain (and tested there) are not yet successful. The effort nevertheless leads to an alternative analysis about how ssz1 ∆ and upf1 ∆ mutations can help prion propagation. The cellular propagation of the yeast prion [ PSI + ] requires appropriate activities of the Hsp104 disaggregase. Many [ PSI + ] variants isolated in wild-type strains cannot propagate in cells expressing Hsp104 T160M , which has weaker activities. Yet another group of [ PSI + ] variants shows the opposite, propagating well with Hsp104 T160M but is eliminated by the wild-type protein. Deletion of SSZ1 and UPF1 genes in Hsp104 T160M cells generates a just-right environment that supports the propagation of both types of [ PSI + ] variants. The pro-prion effect is not due to the removal of active curing by Ssz1 or Upf1–such curing activity is not observed for the variants. Rather, the double deletion causes a cellular response, which enables more efficient fragmentation of prion fibers, thus remedying the weak activity of Hsp104 T160M . The “Goldilocks” conditioning seems also applicable to other yeast prions. Two [ PIN + ] variants that propagate well with wild-type Hsp104 but poorly with Hsp104 ∆N , lacking residues (2-147), can however thrive with the latter if Ssz1 and Upf1 are also deleted from the cell. In this case, the double deletion results in higher Hsp104 ∆N expression, leading to improved generation of prion seeds for robust propagation.
Source: Current Genetics
Author: Chih-Yen King
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Funder: Academia Sinica
OpenAlex ID: W4409039127