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Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation.

ABSTRACT: 6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI(+)] using both PFAR-enriched mutants and site-directed methylation. We demonstrate that PFAR is involved in propagation and de novo formation of [PSI(+)]. PFAR and the yeast heat-shock protein Hsp104 partially compensate each other for [PSI(+)] propagation. Our data also provide insight into new functions for the ribosome in basal thermotolerance and heat-shocked protein refolding. PFAR is thus an evolutionarily conserved cell component implicated in the prion life cycle, and we propose that it could be a potential therapeutic target for human protein misfolding diseases.

SUBMITTER: Blondel M

PROVIDER: S-EPMC5025663 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation.

Blondel Marc M Soubigou Flavie F Evrard Justine J Nguyen Phu Hai PH Hasin Naushaba N Chédin Stéphane S Gillet Reynald R Contesse Marie-Astrid MA Friocourt Gaëlle G Stahl Guillaume G Jones Gary W GW Voisset Cécile C

Scientific reports 20160916

6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI(+)] using both PFAR-enriched mutants and site-directed methylation. We demonstrate that PFAR is involved in propagation and de novo formation of [PSI(+)]. PFAR and the yeast heat-shock protein Hsp104 partially compensate each other ...[more]

PMID: 27633137

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