Protein folding activity of the ribosome is involved in yeast prion propagation

Marc Blondel (1) , Flavie Soubigou (1) , Justine Evrard (1) , Phu Hai Nguyen (1) , Naushaba Hasin (2) , Stéphane Chédin (3) , Reynald Gillet (4) , Marie-Astrid Contesse (1) , Gaëlle Friocourt (1) , Guillaume Stahl (5) , Gary W. Jones (2) , Cécile Voisset (1)

1 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
2 Maynooth University - National University of Ireland Maynooth
3 I2BC - Institut de Biologie Intégrative de la Cellule
4 IGDR - Institut de Génétique et Développement de Rennes
5 LBMCE - Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes

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.

Domaines: Biochimie, Biologie Moléculaire; Organisation et fonctions cellulaires [q-bio.SC]; Neurobiologie

Marc Blondel, Flavie Soubigou, Justine Evrard, Phu Hai Nguyen, Naushaba Hasin, et al.. Protein folding activity of the ribosome is involved in yeast prion propagation. Scientific Reports, 2016, 6, pp.32117. ⟨10.1038/srep32117⟩. ⟨hal-01394774⟩