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Article: Post-transcriptional negative feedback regulation of proteostasis through the Dis3 ribonuclease and its disruption by polyQ-expanded Huntingtin

TitlePost-transcriptional negative feedback regulation of proteostasis through the Dis3 ribonuclease and its disruption by polyQ-expanded Huntingtin
Authors
KeywordsProteins
HSP70 Heat-Shock Proteins
Protein homeostasis
Issue Date2019
PublisherOxford University Press (OUP): Policy C - Option B. The Journal's web site is located at http://nar.oxfordjournals.org/
Citation
Nucleic Acids Research, 2019, v. 47 n. 19, p. 10040-10058 How to Cite?
AbstractWhen proteostasis is disrupted by stresses such as heat shock, the heat stress response will be stimulated, leading to up-regulation of molecular chaperones by transcriptional activation and mRNA stabilization for restoring proteostasis. Although the mechanisms for their transcriptional activation have been clearly defined, how chaperone mRNAs are stabilized remains largely unknown. Starting by exploring the coupling between the apparently unrelated RNA degradation and protein quality control (PQC) systems, we show that the Dis3 ribonuclease, catalytic subunit of the RNA exosome required for RNA degradation, suppresses PQC activity in unstressed cells by degrading mRNAs encoding the Hsp70 cofactors Sis1, Ydj1 and Fes1, as well as some other chaperones or PQC factors, thereby limiting their protein expression. Dis3 is stabilized through its binding to Sis1 and the Hsp70s Ssa1/2. Upon heat stress, loss of Sis1 and Ssa1/2 availability triggers Dis3 ubiquitination and degradation, leading to stabilization of those chaperone mRNAs originally targeted by Dis3. We further demonstrate that polyQ-expanded huntingtin delays Dis3 degradation during heat stress and thus hinders chaperone mRNA stabilization. Our findings not only reveal a post-transcriptional negative feedback loop for maintaining proteostasis, but also uncover a mechanism that contributes to the impaired heat stress response in Huntington's disease.
Persistent Identifierhttp://hdl.handle.net/10722/278072
ISSN
2023 Impact Factor: 16.6
2023 SCImago Journal Rankings: 7.048
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKong, KY-
dc.contributor.authorHUNG, TNF-
dc.contributor.authorMan, PHM-
dc.contributor.authorWONG, TN-
dc.contributor.authorCHENG, T-
dc.contributor.authorJin, DY-
dc.date.accessioned2019-10-04T08:06:58Z-
dc.date.available2019-10-04T08:06:58Z-
dc.date.issued2019-
dc.identifier.citationNucleic Acids Research, 2019, v. 47 n. 19, p. 10040-10058-
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10722/278072-
dc.description.abstractWhen proteostasis is disrupted by stresses such as heat shock, the heat stress response will be stimulated, leading to up-regulation of molecular chaperones by transcriptional activation and mRNA stabilization for restoring proteostasis. Although the mechanisms for their transcriptional activation have been clearly defined, how chaperone mRNAs are stabilized remains largely unknown. Starting by exploring the coupling between the apparently unrelated RNA degradation and protein quality control (PQC) systems, we show that the Dis3 ribonuclease, catalytic subunit of the RNA exosome required for RNA degradation, suppresses PQC activity in unstressed cells by degrading mRNAs encoding the Hsp70 cofactors Sis1, Ydj1 and Fes1, as well as some other chaperones or PQC factors, thereby limiting their protein expression. Dis3 is stabilized through its binding to Sis1 and the Hsp70s Ssa1/2. Upon heat stress, loss of Sis1 and Ssa1/2 availability triggers Dis3 ubiquitination and degradation, leading to stabilization of those chaperone mRNAs originally targeted by Dis3. We further demonstrate that polyQ-expanded huntingtin delays Dis3 degradation during heat stress and thus hinders chaperone mRNA stabilization. Our findings not only reveal a post-transcriptional negative feedback loop for maintaining proteostasis, but also uncover a mechanism that contributes to the impaired heat stress response in Huntington's disease.-
dc.languageeng-
dc.publisherOxford University Press (OUP): Policy C - Option B. The Journal's web site is located at http://nar.oxfordjournals.org/-
dc.relation.ispartofNucleic Acids Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectProteins-
dc.subjectHSP70 Heat-Shock Proteins-
dc.subjectProtein homeostasis-
dc.titlePost-transcriptional negative feedback regulation of proteostasis through the Dis3 ribonuclease and its disruption by polyQ-expanded Huntingtin-
dc.typeArticle-
dc.identifier.emailKong, KY: ewedwin@hku.hk-
dc.identifier.emailJin, DY: dyjin@hku.hk-
dc.identifier.authorityJin, DY=rp00452-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/nar/gkz722-
dc.identifier.pmid31428776-
dc.identifier.pmcidPMC6821268-
dc.identifier.scopuseid_2-s2.0-85074310271-
dc.identifier.hkuros307074-
dc.identifier.volume47-
dc.identifier.issue19-
dc.identifier.spage10040-
dc.identifier.epage10058-
dc.identifier.isiWOS:000496767900016-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl0305-1048-

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