Transcription errors induce proteotoxic stress and shorten cellular lifespan.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Vermulst M,Denney AS,Lang MJ,Hung CW,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,E

doi

10.1038/ncomms9065

subject

Has Abstract

pub_date

2015-08-25 00:00:00

pages

8065

issn

2041-1723

pii

ncomms9065

journal_volume

6

pub_type

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