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Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized
Activation of the integrated stress response (ISR) or the ribosome-associated quality control (RQC) pathway stimulates regulatory ribosomal ubiquitylation (RRub) on distinct 40S ribosomal proteins, yet the cellular role and fate of ubiquitylated proteins remain unclear. We demonstrate that uS10 and...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064338/ https://www.ncbi.nlm.nih.gov/pubmed/32011234 http://dx.doi.org/10.7554/eLife.54023 |
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author | Garshott, Danielle M Sundaramoorthy, Elayanambi Leonard, Marilyn Bennett, Eric J |
author_facet | Garshott, Danielle M Sundaramoorthy, Elayanambi Leonard, Marilyn Bennett, Eric J |
author_sort | Garshott, Danielle M |
collection | PubMed |
description | Activation of the integrated stress response (ISR) or the ribosome-associated quality control (RQC) pathway stimulates regulatory ribosomal ubiquitylation (RRub) on distinct 40S ribosomal proteins, yet the cellular role and fate of ubiquitylated proteins remain unclear. We demonstrate that uS10 and uS5 ubiquitylation are dependent upon eS10 or uS3 ubiquitylation, respectively, suggesting that a hierarchical relationship exists among RRub events establishing a ubiquitin code on ribosomes. We show that stress dependent RRub events diminish after initial stimuli and that demodification by deubiquitylating enzymes contributes to reduced RRub levels during stress recovery. Utilizing an optical RQC reporter we identify OTUD3 and USP21 as deubiquitylating enzymes that antagonize ZNF598-mediated 40S ubiquitylation and can limit RQC activation. Critically, cells lacking USP21 or OTUD3 have altered RQC activity and delayed eS10 deubiquitylation indicating a functional role for deubiquitylating enzymes within the RQC pathway. |
format | Online Article Text |
id | pubmed-7064338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-70643382020-03-11 Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized Garshott, Danielle M Sundaramoorthy, Elayanambi Leonard, Marilyn Bennett, Eric J eLife Cell Biology Activation of the integrated stress response (ISR) or the ribosome-associated quality control (RQC) pathway stimulates regulatory ribosomal ubiquitylation (RRub) on distinct 40S ribosomal proteins, yet the cellular role and fate of ubiquitylated proteins remain unclear. We demonstrate that uS10 and uS5 ubiquitylation are dependent upon eS10 or uS3 ubiquitylation, respectively, suggesting that a hierarchical relationship exists among RRub events establishing a ubiquitin code on ribosomes. We show that stress dependent RRub events diminish after initial stimuli and that demodification by deubiquitylating enzymes contributes to reduced RRub levels during stress recovery. Utilizing an optical RQC reporter we identify OTUD3 and USP21 as deubiquitylating enzymes that antagonize ZNF598-mediated 40S ubiquitylation and can limit RQC activation. Critically, cells lacking USP21 or OTUD3 have altered RQC activity and delayed eS10 deubiquitylation indicating a functional role for deubiquitylating enzymes within the RQC pathway. eLife Sciences Publications, Ltd 2020-02-03 /pmc/articles/PMC7064338/ /pubmed/32011234 http://dx.doi.org/10.7554/eLife.54023 Text en © 2020, Garshott et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Garshott, Danielle M Sundaramoorthy, Elayanambi Leonard, Marilyn Bennett, Eric J Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized |
title | Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized |
title_full | Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized |
title_fullStr | Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized |
title_full_unstemmed | Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized |
title_short | Distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized |
title_sort | distinct regulatory ribosomal ubiquitylation events are reversible and hierarchically organized |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064338/ https://www.ncbi.nlm.nih.gov/pubmed/32011234 http://dx.doi.org/10.7554/eLife.54023 |
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