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dc.contributor.authorMarch, Zachary M.
dc.contributor.authorKing, Oliver D.
dc.contributor.authorShorter, James
dc.date2022-08-11T08:08:03.000
dc.date.accessioned2022-08-23T15:40:54Z
dc.date.available2022-08-23T15:40:54Z
dc.date.issued2016-09-15
dc.date.submitted2016-09-19
dc.identifier.citation<p>Brain Res. 2016 Sep 15;1647:9-18. doi: 10.1016/j.brainres.2016.02.037. Epub 2016 Mar 18. <a href="http://dx.doi.org/10.1016/j.brainres.2016.02.037">Link to article on publisher's site</a></p>
dc.identifier.issn0006-8993 (Linking)
dc.identifier.doi10.1016/j.brainres.2016.02.037
dc.identifier.pmid26996412
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26506
dc.description.abstractKey challenges faced by all cells include how to spatiotemporally organize complex biochemistry and how to respond to environmental fluctuations. The budding yeast Saccharomyces cerevisiae harnesses alternative protein folding mediated by yeast prion domains (PrDs) for rapid evolution of new traits in response to environmental stress. Increasingly, it is appreciated that low complexity domains similar in amino acid composition to yeast PrDs (prion-like domains; PrLDs) found in metazoa have a prominent role in subcellular cytoplasmic organization, especially in relation to RNA homeostasis. In this review, we highlight recent advances in our understanding of the role of prions in enabling rapid adaptation to environmental stress in yeast. We also present the complete list of human proteins with PrLDs and discuss the prevalence of the PrLD in nucleic-acid binding proteins that are often connected to neurodegenerative disease, including: ataxin 1, ataxin 2, FUS, TDP-43, TAF15, EWSR1, hnRNPA1, and hnRNPA2. Recent paradigm-shifting advances establish that PrLDs undergo phase transitions to liquid states, which contribute to the structure and biophysics of diverse membraneless organelles. This structural functionality of PrLDs, however, simultaneously increases their propensity for deleterious protein-misfolding events that drive neurodegenerative disease. We suggest that even these PrLD-misfolding events are not irreversible and can be mitigated by natural or engineered protein disaggregases, which could have important therapeutic applications. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26996412&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectALS
dc.subjectDisaggregase
dc.subjectPhase transition
dc.subjectPrion
dc.subjectPrion-like domains
dc.subjectRNA-binding proteins
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectCell and Developmental Biology
dc.subjectCells
dc.subjectFungi
dc.subjectNervous System Diseases
dc.subjectNeuroscience and Neurobiology
dc.subjectNutritional and Metabolic Diseases
dc.titlePrion-like domains as epigenetic regulators, scaffolds for subcellular organization, and drivers of neurodegenerative disease
dc.typeJournal Article
dc.source.journaltitleBrain research
dc.source.volume1647
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1191&amp;context=cellbiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cellbiology_pp/192
dc.identifier.contextkey9135198
refterms.dateFOA2022-08-23T15:40:55Z
html.description.abstract<p>Key challenges faced by all cells include how to spatiotemporally organize complex biochemistry and how to respond to environmental fluctuations. The budding yeast Saccharomyces cerevisiae harnesses alternative protein folding mediated by yeast prion domains (PrDs) for rapid evolution of new traits in response to environmental stress. Increasingly, it is appreciated that low complexity domains similar in amino acid composition to yeast PrDs (prion-like domains; PrLDs) found in metazoa have a prominent role in subcellular cytoplasmic organization, especially in relation to RNA homeostasis. In this review, we highlight recent advances in our understanding of the role of prions in enabling rapid adaptation to environmental stress in yeast. We also present the complete list of human proteins with PrLDs and discuss the prevalence of the PrLD in nucleic-acid binding proteins that are often connected to neurodegenerative disease, including: ataxin 1, ataxin 2, FUS, TDP-43, TAF15, EWSR1, hnRNPA1, and hnRNPA2. Recent paradigm-shifting advances establish that PrLDs undergo phase transitions to liquid states, which contribute to the structure and biophysics of diverse membraneless organelles. This structural functionality of PrLDs, however, simultaneously increases their propensity for deleterious protein-misfolding events that drive neurodegenerative disease. We suggest that even these PrLD-misfolding events are not irreversible and can be mitigated by natural or engineered protein disaggregases, which could have important therapeutic applications. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.</p>
dc.identifier.submissionpathcellbiology_pp/192
dc.contributor.departmentDepartment of Cell and Developmental Biology
dc.source.pages9-18


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Copyright 2016 The Authors. Published  by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).