| Literature DB >> 26304740 |
Marc Vermulst1,2, Ashley S Denney3, Michael J Lang4, Chao-Wei Hung5, Stephanie Moore1, M Arthur Moseley6, Arthur M Mosely6, J Will Thompson6, William J Thompson6, Victoria Madden7, Jacob Gauer5, Katie J Wolfe8, Daniel W Summers9, Jennifer Schleit10, George L Sutphin10, Suraiya Haroon2, Agnes Holczbauer2, Joanne Caine11, James Jorgenson1, Douglas Cyr8, Matt Kaeberlein10, Jeffrey N Strathern12, Mara C Duncan4, Dorothy A Erie1,13.
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.Entities:
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Year: 2015 PMID： 26304740 PMCID： PMC4684168 DOI： 10.1038/ncomms9065
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919