Rodríguez-Galán, OlgaGarcía-Gómez, Juan J.Rosado, Iván V.Wei, WuMéndez-Godoy, AlfonsoPillet, BenjaminAlekseenko, AlisaSteinmetz, Lars M.Pelechano, VicentKressler, Dieterde la Cruz, Jesús2023-01-112023-01-112020-12-16Rodríguez-Galán O, García-Gómez JJ, Rosado IV, Wei W, Méndez-Godoy A, Pillet B, et al. A functional connection between translation elongation and protein folding at the ribosome exit tunnel in Saccharomyces cerevisiae. Nucleic Acids Res. 2021 Jan 11;49(1):206-2200305-1048http://hdl.handle.net/10668/4574Proteostasis needs to be tightly controlled to meet the cellular demand for correctly de novo folded proteins and to avoid protein aggregation. While a coupling between translation rate and co-translational folding, likely involving an interplay between the ribosome and its associated chaperones, clearly appears to exist, the underlying mechanisms and the contribution of ribosomal proteins remain to be explored. The ribosomal protein uL3 contains a long internal loop whose tip region is in close proximity to the ribosomal peptidyl transferase center. Intriguingly, the rpl3[W255C] allele, in which the residue making the closest contact to this catalytic site is mutated, affects diverse aspects of ribosome biogenesis and function. Here, we have uncovered, by performing a synthetic lethal screen with this allele, an unexpected link between translation and the folding of nascent proteins by the ribosome-associated Ssb-RAC chaperone system. Our results reveal that uL3 and Ssb-RAC cooperate to prevent 80S ribosomes from piling up within the 5' region of mRNAs early on during translation elongation. Together, our study provides compelling in vivo evidence for a functional connection between peptide bond formation at the peptidyl transferase center and chaperone-assisted de novo folding of nascent polypeptides at the solvent-side of the peptide exit tunnel.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/AllelesRibosomesProteostasisMutationSaccharomyces cerevisiaeProtein foldingMolecular chaperonesAlelosRibosomasMutaciónProteínas de saccharomyces cerevisiaePliegue de proteínaChaperonas molecularesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::AllelesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Molecular ChaperonesMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Multiprotein ComplexesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Mutation, MissenseMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Peptide Biosynthesis::Protein Biosynthesis::Peptide Chain Elongation, TranslationalMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Point MutationMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Recombinant ProteinsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Ribosomal ProteinsMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::RibosomesMedical Subject Headings::Organisms::Eukaryota::Fungi::Ascomycota::Saccharomycetales::Saccharomyces::Saccharomyces cerevisiaeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Fungal Proteins::Saccharomyces cerevisiae ProteinsMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Biophysical Phenomena::Biophysical Processes::Protein FoldingMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Acyltransferases::Aminoacyltransferases::Peptidyl TransferasesMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Proteostasis DeficienciesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::SolventsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptidesresearch article33330942open access10.1093/nar/gkaa12001362-4962PMC7797049