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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Biochemistry and Molecular Biology
2021
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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. |
format | Online Article Text |
id | pubmed-8505234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Korean Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
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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