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 Communjournal_title
Nature communicationsauthors
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,Edoi
10.1038/ncomms9065subject
Has Abstractpub_date
2015-08-25 00:00:00pages
8065issn
2041-1723pii
ncomms9065journal_volume
6pub_type
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