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The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology

Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indica...

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Autores principales: Park, Jumin, Park, Jongmin, Lee, Jongbin, Lim, Chunghun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505234/
https://www.ncbi.nlm.nih.gov/pubmed/34488933
http://dx.doi.org/10.5483/BMBRep.2021.54.9.097
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author Park, Jumin
Park, Jongmin
Lee, Jongbin
Lim, Chunghun
author_facet Park, Jumin
Park, Jongmin
Lee, Jongbin
Lim, Chunghun
author_sort Park, Jumin
collection PubMed
description Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indication of atypical translation. The ribosome-associated E3 ligase ZNF598 ubiquitinates small subunit proteins at the stalled ribosomes. A series of RQC factors are then recruited to dissociate and triage aberrant translation intermediates. Regulatory ribosomal stalling may occur on endogenous transcripts for quality gene expression, whereas ribosomal collisions are more globally induced by ribotoxic stressors such as translation inhibitors, ribotoxins, and UV radiation. The latter are sensed by ribosome-associated kinases GCN2 and ZAKα, activating integrated stress response (ISR) and ribotoxic stress response (RSR), respectively. Hierarchical crosstalks among RQC, ISR, and RSR pathways are readily detectable since the collided ribosome is their common substrate for activation. Given the strong implications of RQC factors in neuronal physiology and neurological disorders, the interplay between RQC and ribosome-associated stress signaling may sustain proteostasis, adaptively determine cell fate, and contribute to neural pathogenesis. The elucidation of underlying molecular principles in relevant human diseases should thus provide unexplored therapeutic opportunities.
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spelling pubmed-85052342021-10-22 The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology Park, Jumin Park, Jongmin Lee, Jongbin Lim, Chunghun BMB Rep Invited Mini Review Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indication of atypical translation. The ribosome-associated E3 ligase ZNF598 ubiquitinates small subunit proteins at the stalled ribosomes. A series of RQC factors are then recruited to dissociate and triage aberrant translation intermediates. Regulatory ribosomal stalling may occur on endogenous transcripts for quality gene expression, whereas ribosomal collisions are more globally induced by ribotoxic stressors such as translation inhibitors, ribotoxins, and UV radiation. The latter are sensed by ribosome-associated kinases GCN2 and ZAKα, activating integrated stress response (ISR) and ribotoxic stress response (RSR), respectively. Hierarchical crosstalks among RQC, ISR, and RSR pathways are readily detectable since the collided ribosome is their common substrate for activation. Given the strong implications of RQC factors in neuronal physiology and neurological disorders, the interplay between RQC and ribosome-associated stress signaling may sustain proteostasis, adaptively determine cell fate, and contribute to neural pathogenesis. The elucidation of underlying molecular principles in relevant human diseases should thus provide unexplored therapeutic opportunities. Korean Society for Biochemistry and Molecular Biology 2021-09-30 2021-09-30 /pmc/articles/PMC8505234/ /pubmed/34488933 http://dx.doi.org/10.5483/BMBRep.2021.54.9.097 Text en Copyright © 2021 by the The Korean Society for Biochemistry and Molecular Biology https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Invited Mini Review
Park, Jumin
Park, Jongmin
Lee, Jongbin
Lim, Chunghun
The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology
title The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology
title_full The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology
title_fullStr The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology
title_full_unstemmed The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology
title_short The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology
title_sort trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology
topic Invited Mini Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505234/
https://www.ncbi.nlm.nih.gov/pubmed/34488933
http://dx.doi.org/10.5483/BMBRep.2021.54.9.097
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