Transcription errors induce proteotoxic stress and shorten cellular lifespan.
Journal Article (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
- PMC4684168
Electronic International Standard Serial Number (EISSN)
- 2041-1723
Digital Object Identifier (DOI)
- 10.1038/ncomms9065
Language
- eng
Conference Location
- England