A functional connection between translation elongation and protein folding at the ribosome exit tunnel in Saccharomyces cerevisiae.
Alleles
Loss of Function Mutation
Molecular Chaperones
/ genetics
Multiprotein Complexes
/ physiology
Mutation, Missense
Peptide Chain Elongation, Translational
/ physiology
Peptidyl Transferases
/ physiology
Point Mutation
Protein Folding
Proteostasis
/ physiology
Recombinant Proteins
/ metabolism
Ribosomal Proteins
/ genetics
Ribosomes
/ metabolism
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
11 01 2021
11 01 2021
Historique:
accepted:
14
12
2020
revised:
18
11
2020
received:
19
10
2020
pubmed:
18
12
2020
medline:
23
1
2021
entrez:
17
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33330942
pii: 6039917
doi: 10.1093/nar/gkaa1200
pmc: PMC7797049
doi:
Substances chimiques
Molecular Chaperones
0
Multiprotein Complexes
0
Recombinant Proteins
0
Ribosomal Proteins
0
Rpl3 protein, S cerevisiae
0
Saccharomyces cerevisiae Proteins
0
Peptidyl Transferases
EC 2.3.2.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
206-220Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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