Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway

Transcription by RNA polymerase III (Pol III) is an essential cellular process, and mutations in Pol III can cause neurodegenerative disease in humans. However, in contrast to Pol II transcription, which has been extensively studied, the knowledge of how Pol III is regulated is very limited. We repo...

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Main Authors: Zheng Wang, Catherine Wu, Aaron Aslanian, John R Yates III, Tony Hunter
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/35447
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spelling doaj-7a2ad5122dc54cff84003af4e0de6ef02021-05-05T16:08:24ZengeLife Sciences Publications LtdeLife2050-084X2018-09-01710.7554/eLife.35447Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathwayZheng Wang0Catherine Wu1Aaron Aslanian2John R Yates III3Tony Hunter4https://orcid.org/0000-0002-7691-6993Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United StatesMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United StatesMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States; The Scripps Research Institute, La Jolla, United StatesThe Scripps Research Institute, La Jolla, United StatesMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United StatesTranscription by RNA polymerase III (Pol III) is an essential cellular process, and mutations in Pol III can cause neurodegenerative disease in humans. However, in contrast to Pol II transcription, which has been extensively studied, the knowledge of how Pol III is regulated is very limited. We report here that in budding yeast, Saccharomyces cerevisiae, Pol III is negatively regulated by the Small Ubiquitin-like MOdifier (SUMO), an essential post-translational modification pathway. Besides sumoylation, Pol III is also targeted by ubiquitylation and the Cdc48/p97 segregase; these three processes likely act in a sequential manner and eventually lead to proteasomal degradation of Pol III subunits, thereby repressing Pol III transcription. This study not only uncovered a regulatory mechanism for Pol III, but also suggests that the SUMO and ubiquitin modification pathways and the Cdc48/p97 segregase can be potential therapeutic targets for Pol III-related human diseases.https://elifesciences.org/articles/35447SUMOUbiquitinneurodegenerationpost-translational modificationquality controltranscription
collection DOAJ
language English
format Article
sources DOAJ
author Zheng Wang
Catherine Wu
Aaron Aslanian
John R Yates III
Tony Hunter
spellingShingle Zheng Wang
Catherine Wu
Aaron Aslanian
John R Yates III
Tony Hunter
Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway
eLife
SUMO
Ubiquitin
neurodegeneration
post-translational modification
quality control
transcription
author_facet Zheng Wang
Catherine Wu
Aaron Aslanian
John R Yates III
Tony Hunter
author_sort Zheng Wang
title Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway
title_short Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway
title_full Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway
title_fullStr Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway
title_full_unstemmed Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway
title_sort defective rna polymerase iii is negatively regulated by the sumo-ubiquitin-cdc48 pathway
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2018-09-01
description Transcription by RNA polymerase III (Pol III) is an essential cellular process, and mutations in Pol III can cause neurodegenerative disease in humans. However, in contrast to Pol II transcription, which has been extensively studied, the knowledge of how Pol III is regulated is very limited. We report here that in budding yeast, Saccharomyces cerevisiae, Pol III is negatively regulated by the Small Ubiquitin-like MOdifier (SUMO), an essential post-translational modification pathway. Besides sumoylation, Pol III is also targeted by ubiquitylation and the Cdc48/p97 segregase; these three processes likely act in a sequential manner and eventually lead to proteasomal degradation of Pol III subunits, thereby repressing Pol III transcription. This study not only uncovered a regulatory mechanism for Pol III, but also suggests that the SUMO and ubiquitin modification pathways and the Cdc48/p97 segregase can be potential therapeutic targets for Pol III-related human diseases.
topic SUMO
Ubiquitin
neurodegeneration
post-translational modification
quality control
transcription
url https://elifesciences.org/articles/35447
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