Transcription errors induce proteotoxic stress and shorten cellular lifespan

Marc Vermulst, Ashley S. Denney, Michael J. Lang, Chao Wei Hung, Stephanie Moore, Arthur M. Mosely, William J. Thompson, Victoria Madden, Jacob Gauer, Katie J. Wolfe, Daniel W. Summers, Jennifer Schleit, George L. Sutphin, Suraiya Haroon, Agnes Holczbauer, Joanne Caine, James Jorgenson, Douglas Cyr, Matt Kaeberlein, Jeffrey N. StrathernMara C. Duncan, Dorothy A. Erie

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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.

Original languageEnglish (US)
Article number8065
JournalNature communications
Volume6
DOIs
StatePublished - Aug 25 2015
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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