Transcription errors induce proteotoxic stress and shorten cellular lifespan.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • August 25, 2015

Published In

Volume / Issue

  • 6 /

Start / End Page

  • 8065 -

PubMed ID

  • 26304740

Pubmed Central ID

  • 26304740

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms9065

Language

  • eng