Title | Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Tye, BW, Commins, N, Ryazanova, LV, Wühr, M, Springer, M, Pincus, D, L Churchman, S |
Journal | Elife |
Volume | 8 |
Date Published | 2019 Mar 07 |
ISSN | 2050-084X |
Keywords | Microbial Viability, Organelle Biogenesis, Protein Aggregation, Pathological, Protein Biosynthesis, Proteostasis, Ribosomal Proteins, Ribosomes, RNA, Ribosomal, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins |
Abstract | <p>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 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.</p> |
DOI | 10.7554/eLife.43002 |
Alternate Journal | Elife |
PubMed ID | 30843788 |
PubMed Central ID | PMC6453566 |
Grant List | R01-HG007173 / NH / NIH HHS / United States R01-GM120122 / NH / NIH HHS / United States DE-SC0018420 / / Department of Energy, Labor and Economic Growth / International R01-GM117333 / NH / NIH HHS / United States 2013171680 / / National Science Foundation / International R35 GM128813 / GM / NIGMS NIH HHS / United States R01 GM120122 / GM / NIGMS NIH HHS / United States R35-GM128813 / NH / NIH HHS / United States R01 GM117333 / GM / NIGMS NIH HHS / United States R01 HG007173 / HG / NHGRI NIH HHS / United States |