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Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness

Author(s): Tye, Blake W; Commins, Nicoletta; Ryazanova, Lillia V; Wühr, Martin; Springer, Michael; et al

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Abstract: To achieve maximal growth, cells must manage a massive economy of ribosomal proteins (r-proteins) and RNAs (rRNAs) to produce thousands of ribosomes every minute. Although ribosomes are essential in all cells, natural disruptions to ribosome biogenesis lead to heterogeneous phenotypes. Here, we model these perturbations in Saccharomyces cerevisiae and show that challenges to ribosome biogenesis result in acute loss of proteostasis. Imbalances in the synthesis of r-proteins and rRNAs lead to the rapid aggregation of newly synthesized orphan r-proteins and compromise essential cellular processes, which cells alleviate by activating proteostasis genes. Exogenously bolstering the proteostasis network increases cellular fitness in the face of challenges to ribosome assembly, demonstrating the direct contribution of orphan r-proteins to cellular phenotypes. We propose that ribosome assembly is a key vulnerability of proteostasis maintenance in proliferating cells that may be compromised by diverse genetic, environmental, and xenobiotic perturbations that generate orphan r-proteins.
Publication Date: 7-Mar-2019
Citation: Tye, Blake W, Commins, Nicoletta, Ryazanova, Lillia V, Wühr, Martin, Springer, Michael, Pincus, David, Churchman, L Stirling. (2019). Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness. eLife, 8 (10.7554/elife.43002)
DOI: doi:10.7554/elife.43002
ISSN: 2050-084X
EISSN: 2050-084X
Pages: e43002 - e43002
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: eLife
Version: Final published version. This is an open access article.

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