Ribosome-associated quality-control mechanisms from bacteria to humans.
C-terminal tail
CAT tail
KLHDC10
LTN1
Listerin
NEMF
Pirh2
RQC
Rqc2
RqcH
alanine tail
quality control
ribosome
ribosome collision
ribosome stalling
translation
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
21 04 2022
21 04 2022
Historique:
received:
24
01
2022
revised:
23
03
2022
accepted:
28
03
2022
entrez:
22
4
2022
pubmed:
23
4
2022
medline:
27
4
2022
Statut:
ppublish
Résumé
Ribosome-associated quality-control (RQC) surveys incomplete nascent polypeptides produced by interrupted translation. Central players in RQC are the human ribosome- and tRNA-binding protein, NEMF, and its orthologs, yeast Rqc2 and bacterial RqcH, which sense large ribosomal subunits obstructed with nascent chains and then promote nascent-chain proteolysis. In canonical eukaryotic RQC, NEMF stabilizes the LTN1/Listerin E3 ligase binding to obstructed ribosomal subunits for nascent-chain ubiquitylation. Furthermore, NEMF orthologs across evolution modify nascent chains by mediating C-terminal, untemplated polypeptide elongation. In eukaryotes, this process exposes ribosome-buried nascent-chain lysines, the ubiquitin acceptor sites, to LTN1. Remarkably, in both bacteria and eukaryotes, C-terminal tails also have an extra-ribosomal function as degrons. Here, we discuss recent findings on RQC mechanisms and briefly review how ribosomal stalling is sensed upstream of RQC, including via ribosome collisions, from an evolutionary perspective. Because RQC defects impair cellular fitness and cause neurodegeneration, this knowledge provides a framework for pathway-related biology and disease studies.
Identifiants
pubmed: 35452614
pii: S1097-2765(22)00294-5
doi: 10.1016/j.molcel.2022.03.038
pmc: PMC9034055
mid: NIHMS1798005
pii:
doi:
Substances chimiques
Peptides
0
Saccharomyces cerevisiae Proteins
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1451-1466Subventions
Organisme : NINDS NIH HHS
ID : R01 NS102414
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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