RT Journal Article
T1 A functional connection between translation elongation and protein folding at the ribosome exit tunnel in Saccharomyces cerevisiae
A1 Rodríguez-Galán, Olga
A1 García-Gómez, Juan J.
A1 Rosado, Iván V.
A1 Wei, Wu
A1 Méndez-Godoy, Alfonso
A1 Pillet, Benjamin
A1 Alekseenko, Alisa
A1 Steinmetz, Lars M.
A1 Pelechano, Vicent
A1 Kressler, Dieter
A1 de la Cruz, Jesús
K1 Alleles
K1 Ribosomes
K1 Proteostasis
K1 Mutation
K1 Saccharomyces cerevisiae
K1 Protein folding
K1 Molecular chaperones
K1 Alelos
K1 Ribosomas
K1 Mutación
K1 Proteínas de saccharomyces cerevisiae
K1 Pliegue de proteína
K1 Chaperonas moleculares
AB Proteostasis 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.
PB Oxford University Presss on behalf of Nucleic Acids Research.
SN 0305-1048
YR 2020
FD 2020-12-16
LK http://hdl.handle.net/10668/4574
UL http://hdl.handle.net/10668/4574
LA en
NO Rodríguez-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):206-220
DS RISalud
RD Apr 10, 2025