Journal article
Transcription errors induce proteotoxic stress and shorten cellular lifespan
Nature communications, Vol.6(1), 8065
08/25/2015
DOI: 10.1038/ncomms9065
PMCID: PMC4684168
PMID: 26304740
Abstract
Transcription errors occur in all living cells; however, it is unknown how these errors affect cellular health. To answer this question, we monitor yeast cells that are genetically engineered to display error-prone transcription. We discover that these cells suffer from a profound loss in proteostasis, which sensitizes them to the expression of genes that are associated with protein-folding diseases in humans; thus, transcription errors represent a new molecular mechanism by which cells can acquire disease phenotypes. We further find that the error rate of transcription increases as cells age, suggesting that transcription errors affect proteostasis particularly in aging cells. Accordingly, transcription errors accelerate the aggregation of a peptide that is implicated in Alzheimer's disease, and shorten the lifespan of cells. These experiments reveal a previously unappreciated role for transcriptional fidelity in cellular health and aging.
Details
- Title: Subtitle
- Transcription errors induce proteotoxic stress and shorten cellular lifespan
- Creators
- Marc Vermulst - Children's Hospital of PhiladelphiaAshley S Denney - University of Colorado DenverMichael J Lang - University of MichiganChao-Wei Hung - University of North Carolina at Chapel HillStephanie Moore - University of North Carolina at Chapel HillM Arthur Moseley - Proteomics Core Facility, Duke University, Durham, North Carolina 27710, USAJ Will Thompson - Duke UniversityVictoria Madden - University of North Carolina at Chapel HillJacob Gauer - University of North Carolina at Chapel HillKatie J Wolfe - University of North Carolina at Chapel HillDaniel W Summers - Washington University in St. LouisJennifer Schleit - University of WashingtonGeorge L Sutphin - University of WashingtonSuraiya Haroon - Children's Hospital of PhiladelphiaAgnes Holczbauer - Children's Hospital of PhiladelphiaJoanne Caine - CSIRO, Department of Materials Science and Engineering, Parkville 3052, AustraliaJames Jorgenson - University of North Carolina at Chapel HillDouglas Cyr - University of North Carolina at Chapel HillMatt Kaeberlein - University of WashingtonJeffrey N Strathern - National Cancer InstituteMara C Duncan - University of MichiganDorothy A Erie - University of Michigan
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.6(1), 8065
- DOI
- 10.1038/ncomms9065
- PMID
- 26304740
- PMCID
- PMC4684168
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- England
- Grant note
- GM092741 / NIGMS NIH HHS R01 GM092741 / NIGMS NIH HHS R01 GM067785 / NIGMS NIH HHS R01GM56981 / NIGMS NIH HHS R01 GM080294 / NIGMS NIH HHS GM 080294 / NIGMS NIH HHS T32AG000057 / NIA NIH HHS NIA 11006596 / PHS HHS Intramural NIH HHS R01AG039390 / NIA NIH HHS T32ES007032 / NIEHS NIH HHS R01 GM079480 / NIGMS NIH HHS T32 GM008570 / NIGMS NIH HHS P30 AG013280 / NIA NIH HHS
- Language
- English
- Date published
- 08/25/2015
- Academic Unit
- Iowa Neuroscience Institute; Biology
- Record Identifier
- 9983992050802771
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