title: The double life of the ribosome: When its protein folding activity supports prion propagation.
abstract: It is no longer necessary to demonstrate that ribosome is the central machinery of protein synthesis. But it is less known that it is also key player of the protein folding process through another conserved function: the protein folding activity of the ribosome (PFAR). This ribozyme activity, discovered more than 2 decades ago, depends upon the domain V of the large rRNA within the large subunit of the ribosome. Surprisingly, we discovered that anti-prion compounds are also potent PFAR inhibitors, highlighting an unexpected link between PFAR and prion propagation. In this review, we discuss the ancestral origin of PFAR in the light of the ancient RNA world hypothesis. We also consider how this ribosomal activity fits into the landscape of cellular protein chaperones involved in the appearance and propagation of prions and other amyloids in mammals. Finally, we examine how drugs targeting the protein folding activity of the ribosome could be active against mammalian prion and other protein aggregation-based diseases, making PFAR a promising therapeutic target for various human protein misfolding diseases.
authors.affiliation: a Inserm UMR 1078 , Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé, Etablissement Français du Sang (EFS) Bretagne, CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire , Brest , France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Voisset
authors.affiliation: a Inserm UMR 1078 , Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé, Etablissement Français du Sang (EFS) Bretagne, CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire , Brest , France.
authors.forename: Marc
authors.initials: M
authors.lastname: Blondel
authors.affiliation: b School of Clinical and Applied Sciences , Faculty of Health and Social Sciences, Leeds Beckett University , Leeds , UK.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jones
authors.affiliation: a Inserm UMR 1078 , Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé, Etablissement Français du Sang (EFS) Bretagne, CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire , Brest , France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Friocourt
authors.affiliation: c Laboratoire de Biologie Moléculaire Eucaryotes , CNRS, Université de Toulouse , Toulouse , France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Stahl
authors.affiliation: d Institute for Integrative Biology of the Cell (I2BC), UMR 9198, CEA, CNRS, Université Paris-Sud, CEA/Saclay, SBIGeM , Gif-sur-Yvette , France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chédin
authors.affiliation: e VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
authors.affiliation: f Université de Rennes 1, CNRS UMR 6290 IGDR , Rennes , France.
authors.forename: Reynald
authors.initials: R
authors.lastname: Gillet
mesh_terms: D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D014176:Protein Biosynthesis; D017510:Protein Folding; D012335:RNA, Ribosomal / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism* / Q000473:pathology*
chemical_list: D006360:Heat-Shock Proteins; D011328:Prions; D012335:RNA, Ribosomal
keywords: PFAR; RNA; chaperon; prion; protein folding; ribosome