Artículo
A functional connection between translation elongation and protein folding at the ribosome exit tunnel in Saccharomyces cerevisiae
Autor/es | Rodríguez Galán, Olga
García Gómez, Juan José Valle Rosado, Iván Wei, Wu Méndez-Godoy, Alfonso Pillet, Benjamin Alekseenko, Alisa Steinmetz, Lars M. Pelechano, Vicent Kressler, Dieter Cruz Díaz, Jesús de la |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2021 |
Fecha de depósito | 2021-09-14 |
Publicado en |
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Resumen | 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 ... 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. |
Identificador del proyecto | BFU2016-75352-P
PID2019-103850-GBI00 31003A-156764 31003A-175547 VR2016-01842 2017YFC0908405 P01 HG000205 1422/4-1 |
Cita | Rodríguez Galán, O., García Gómez, J.J., Valle Rosado, I., Wei, W., Méndez-Godoy, A., Pillet, B.,...,Cruz Díaz, J.d.l. (2021). A functional connection between translation elongation and protein folding at the ribosome exit tunnel in Saccharomyces cerevisiae. Nucleic Acids Research, 49 (1), 206-220. |
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