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Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction
(1) Background: Numerous prions exist in the budding yeast, including [SWI(+)], the prion form of Swi1—a subunit of the chromatin-remodeling complex SWI/SNF. Despite decades of research, the molecular mechanisms underlying prion initiation and propagation are not fully understood. In this study, we...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321512/ https://www.ncbi.nlm.nih.gov/pubmed/35891348 http://dx.doi.org/10.3390/v14071366 |
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author | Du, Zhiqiang Cho, Brandon Li, Liming |
author_facet | Du, Zhiqiang Cho, Brandon Li, Liming |
author_sort | Du, Zhiqiang |
collection | PubMed |
description | (1) Background: Numerous prions exist in the budding yeast, including [SWI(+)], the prion form of Swi1—a subunit of the chromatin-remodeling complex SWI/SNF. Despite decades of research, the molecular mechanisms underlying prion initiation and propagation are not fully understood. In this study, we aimed to identify endogenous cellular proteins that destabilize [SWI(+)]. (2) Methods: We screened the MoBY-ORF 2.0 library for proteins that destabilize [SWI(+)] upon overproduction. We further explored the effects of the identified candidates against other yeast prions and analyzed their potential prion-curing mechanisms. (3) Results: Eighty-two [SWI(+)] suppressors were identified, and their effects were shown to be [SWI(+)]-specific. Interestingly, a few documented [SWI(+)] suppressors were not among the identified hits. Further experiments indicate that, for some of these [SWI(+)] suppressors, their overproduction, and thus their prion-curing activities, are regulated by environmental conditions. Bioinformatics analyses show that our identified [SWI(+)] suppressors are involved in diverse biological functions, with gene ontology term enrichments specifically for transcriptional regulation and translation. Competition for Swi1 monomers between [SWI(+)] and Swi1 interactors, including the SWI/SNF complex, is a potential prion-curing mechanism. (4) Conclusions: We identified a number of [SWI(+)]-specific suppressors that highlight unique features of [SWI(+)] in maintaining its self-perpetuating conformations. |
format | Online Article Text |
id | pubmed-9321512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93215122022-07-27 Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction Du, Zhiqiang Cho, Brandon Li, Liming Viruses Article (1) Background: Numerous prions exist in the budding yeast, including [SWI(+)], the prion form of Swi1—a subunit of the chromatin-remodeling complex SWI/SNF. Despite decades of research, the molecular mechanisms underlying prion initiation and propagation are not fully understood. In this study, we aimed to identify endogenous cellular proteins that destabilize [SWI(+)]. (2) Methods: We screened the MoBY-ORF 2.0 library for proteins that destabilize [SWI(+)] upon overproduction. We further explored the effects of the identified candidates against other yeast prions and analyzed their potential prion-curing mechanisms. (3) Results: Eighty-two [SWI(+)] suppressors were identified, and their effects were shown to be [SWI(+)]-specific. Interestingly, a few documented [SWI(+)] suppressors were not among the identified hits. Further experiments indicate that, for some of these [SWI(+)] suppressors, their overproduction, and thus their prion-curing activities, are regulated by environmental conditions. Bioinformatics analyses show that our identified [SWI(+)] suppressors are involved in diverse biological functions, with gene ontology term enrichments specifically for transcriptional regulation and translation. Competition for Swi1 monomers between [SWI(+)] and Swi1 interactors, including the SWI/SNF complex, is a potential prion-curing mechanism. (4) Conclusions: We identified a number of [SWI(+)]-specific suppressors that highlight unique features of [SWI(+)] in maintaining its self-perpetuating conformations. MDPI 2022-06-23 /pmc/articles/PMC9321512/ /pubmed/35891348 http://dx.doi.org/10.3390/v14071366 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Du, Zhiqiang Cho, Brandon Li, Liming Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
title | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
title_full | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
title_fullStr | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
title_full_unstemmed | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
title_short | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
title_sort | identifying endogenous cellular proteins destabilizing the propagation of swi1 prion upon overproduction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321512/ https://www.ncbi.nlm.nih.gov/pubmed/35891348 http://dx.doi.org/10.3390/v14071366 |
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