The genetic basis of aneuploidy tolerance in wild yeast
- University of Wisconsin-Madison, United States
Abstract
Aneuploidy is highly detrimental during development yet common in cancers and pathogenic fungi – what gives rise to differences in aneuploidy tolerance remains unclear. We previously showed that wild isolates of Saccharomyces cerevisiae tolerate chromosome amplification while laboratory strains used as a model for aneuploid syndromes do not. Here, we mapped the genetic basis to Ssd1, an RNA-binding translational regulator that is functional in wild aneuploids but defective in laboratory strain W303. Loss of SSD1 recapitulates myriad aneuploidy signatures previously taken as eukaryotic responses. We show that aneuploidy tolerance is enabled via a role for Ssd1 in mitochondrial physiology, including binding and regulating nuclear-encoded mitochondrial mRNAs, coupled with a role in mitigating proteostasis stress. Recapitulating ssd1D defects with combinatorial drug treatment selectively blocked proliferation of wild-type aneuploids compared to euploids. Our work adds to elegant studies in the sensitized laboratory strain to present a mechanistic understanding of eukaryotic aneuploidy tolerance.
Data availability
Sequencing data for genetic mapping are available in the Short Read Archive (SRA) under access number PRJNA548343, and MULTIPOOL output files are available in Dataset 1. RNA and RNA Immunoprecipitation (RIP) sequencing data are available from the GEO database under accession number GSE132425, and processed data are also available in Dataset 2. Raw proteomic data are available in the PRIDE database (Project accession # PXD013847); processed data are available in Dataset 2, and normalized protein abundance data are available in Dataset 3.
Article and author information
Author details
Funding
National Cancer Institute ((R01CA229532)
- Audrey P Gasch
Department of Energy (DE-SC0018409)
- Joshua J Coon
- Audrey P Gasch
National Institutes of Health (P41 GM108538)
- Joshua J Coon
National Institutes of Health (T32 GM007133)
- H Auguste Dutcher
National Institutes of Health (T32 HG002760)
- DeElegant Robinson
National Science Foundation (GRFP)
- Leah E Escalante
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hannah Klein, New York University School of Medicine, United States
Version history
- Received: September 20, 2019
- Accepted: January 7, 2020
- Accepted Manuscript published: January 7, 2020 (version 1)
- Version of Record published: January 20, 2020 (version 2)
Copyright
© 2020, Hose et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The genetic basis of aneuploidy tolerance in wild yeast
eLife 9:e52063.
https://doi.org/10.7554/eLife.52063
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