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Transcription errors induce proteotoxic stress and shorten cellular lifespan.

Publication ,  Journal Article
Vermulst, M; Denney, AS; Lang, MJ; Hung, C-W; Moore, S; Moseley, MA; Thompson, JW; Madden, V; Gauer, J; Wolfe, KJ; Summers, DW; Schleit, J ...
Published in: Nat Commun
August 25, 2015
Published version (DOI) Link to item

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.

Duke Scholars

Martin Arthur Moseley III
Author Martin Arthur Moseley III Cell Biology
J. Will Thompson
Author J. Will Thompson Pharmacology & Cancer Biology
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Published In

Nat Commun

DOI

10.1038/ncomms9065

EISSN

2041-1723

Publication Date

August 25, 2015

Volume

6

Start / End Page

8065

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Stress, Physiological
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • RNA Polymerase II
  • Protein Aggregation, Pathological
  • Mutation
  • Molecular Chaperones
  • Heat-Shock Proteins
  • Cellular Senescence
 

Citation

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Vermulst, M., Denney, A. S., Lang, M. J., Hung, C.-W., Moore, S., Moseley, M. A., … Erie, D. A. (2015). Transcription errors induce proteotoxic stress and shorten cellular lifespan. Nat Commun, 6, 8065. https://doi.org/10.1038/ncomms9065
Vermulst, Marc, Ashley S. Denney, Michael J. Lang, Chao-Wei Hung, Stephanie Moore, M Arthur Moseley, J Will Thompson, et al. “Transcription errors induce proteotoxic stress and shorten cellular lifespan.” Nat Commun 6 (August 25, 2015): 8065. https://doi.org/10.1038/ncomms9065.
Vermulst M, Denney AS, Lang MJ, Hung C-W, Moore S, Moseley MA, et al. Transcription errors induce proteotoxic stress and shorten cellular lifespan. Nat Commun. 2015 Aug 25;6:8065.
Vermulst, Marc, et al. “Transcription errors induce proteotoxic stress and shorten cellular lifespan.” Nat Commun, vol. 6, Aug. 2015, p. 8065. Pubmed, doi:10.1038/ncomms9065.
Vermulst M, Denney AS, Lang MJ, Hung C-W, Moore S, Moseley MA, Thompson JW, Madden V, Gauer J, Wolfe KJ, Summers DW, Schleit J, Sutphin GL, Haroon S, Holczbauer A, Caine J, Jorgenson J, Cyr D, Kaeberlein M, Strathern JN, Duncan MC, Erie DA. Transcription errors induce proteotoxic stress and shorten cellular lifespan. Nat Commun. 2015 Aug 25;6:8065.

Published In

Nat Commun

DOI

10.1038/ncomms9065

EISSN

2041-1723

Publication Date

August 25, 2015

Volume

6

Start / End Page

8065

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Stress, Physiological
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • RNA Polymerase II
  • Protein Aggregation, Pathological
  • Mutation
  • Molecular Chaperones
  • Heat-Shock Proteins
  • Cellular Senescence