期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 29, 页码 17031-17040出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2005648117
关键词
aneuploidy; ESR; CAGE; ribosome loss
资金
- NIH [R35 GM118066]
- National Human Genome Research Institute [T32 HG-00035]
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences [P41 GM103533]
Aneuploidy, a condition characterized by whole chromosome gains and losses, is often associated with significant cellular stress and decreased fitness. However, how cells respond to the aneuploid state has remained controversial. In aneuploid budding yeast, two opposing gene-expression patterns have been reported: the environmental stress response (ESR) and the com-mon aneuploidy gene-expression (CAGE) signature, in which many ESR genes are oppositely regulated. Here, we investigate this controversy. We show that the CAGE signature is not an aneuploidy-specific gene-expression signature but the result of normalizing the gene-expression profile of actively proliferating aneuploid cells to that of euploid cells grown into stationary phase. Because growth into stationary phase is among the stron-gest inducers of the ESR, the ESR in aneuploid cells was masked when stationary phase euploid cells were used for normalization in transcriptomic studies. When exponentially growing euploid cells are used in gene-expression comparisons with aneuploid cells, the CAGE signature is no longer evident in aneuploid cells. Instead, aneuploid cells exhibit the ESR. We further show that the ESR causes selective ribosome loss in aneuploid cells, providing an explanation for the decreased cellular density of aneuploid cells. We conclude that aneuploid budding yeast cells mount the ESR, rather than the CAGE signature, in response to aneuploidy-induced cellular stresses, resulting in selective ribosome loss. We propose that the ESR serves two purposes in aneuploid cells: pro-tecting cells from aneuploidy-induced cellular stresses and pre-venting excessive cellular enlargement during slowed cell cycles by down-regulating translation capacity.
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