Innate immunity to yeast prions: Btn2p and Cur1p curing of the [URE3] prion is prevented by 60S ribosomal protein deficiency or ubiquitin/proteasome system overactivity.

[URE3] is an amyloid-based prion of Ure2p, a negative regulator of poor nitrogen source catabolism in Saccharomyces cerevisiae. Overproduced Btn2p or its paralog Cur1p, in processes requiring Hsp42, cure the [URE3] prion. Btn2p cures by collecting Ure2p amyloid filaments at one place in the cell. We find that rpl4a?, rpl21a?, ...
rpl21b?, rpl11b?, and rpl16b? (large ribosomal subunit proteins) or ubr2? (ubiquitin ligase targeting Rpn4p, an activator of proteasome genes) reduce curing by overproduced Btn2p or Cur1p. Impaired curing in ubr2? or rpl21b? is restored by an rpn4? mutation. No effect of rps14a? or rps30b? on curing was observed, indicating that 60S subunit deficiency specifically impairs curing. Levels of Hsp42p, Sis1p, or Btn3p are unchanged in rpl4a?, rpl21b?, or ubr2? mutants. Overproduction of Cur1p or Btn2p was enhanced in rpn4? and hsp42? mutants, lower in ubr2? strains, and restored to above wild-type levels in rpn4? ubr2? strains. As in the wild-type, Ure2N-GFP colocalizes with Btn2-RFP in rpl4a?, rpl21b?, or ubr2? strains, but not in hsp42?. Btn2p/Cur1p overproduction cures [URE3] variants with low seed number, but seed number is not increased in rpl4a?, rpl21b? or ubr2? mutants. Knockouts of genes required for the protein sorting function of Btn2p did not affect curing of [URE3], nor did inactivation of the Hsp104 prion-curing activity. Overactivity of the ubiquitin/proteasome system, resulting from 60S subunit deficiency or ubr2?, may impair Cur1p and Btn2p curing of [URE3] by degrading Cur1p, Btn2p or another component of these curing systems.
Genetics
Date: Apr. 15, 2021
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