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Reference - PMID:25543137 - Dicer and Hsp104 function in a negative feedback loop to confer robustness to environmental stress.

Reference summary

PubMed ID
PMID:25543137
Title
Dicer and Hsp104 function in a negative feedback loop to confer robustness to environmental stress.
Authors
Oberti D, Biasini A, Kirschmann MA, Genoud C, Stunnenberg R, Shimada Y, Bühler M
Citation
Cell Rep 2015 Jan 06;10(1):47-61
Publication year
2015
Abstract
Epigenetic mechanisms can be influenced by environmental cues and thus evoke phenotypic variation. This plasticity can be advantageous for adaptation but also detrimental if not tightly controlled. Although having attracted considerable interest, it remains largely unknown if and how environmental cues such as temperature trigger epigenetic alterations. Using fission yeast, we demonstrate that environmentally induced discontinuous phenotypic variation is buffered by a negative feedback loop that involves the RNase Dicer and the protein disaggregase Hsp104. In the absence of Hsp104, Dicer accumulates in cytoplasmic inclusions and heterochromatin becomes unstable at elevated temperatures, an epigenetic state inherited for many cell divisions after the heat stress. Loss of Dicer leads to toxic aggregation of an exogenous prionogenic protein. Our results highlight the importance of feedback regulation in building epigenetic memory and uncover Hsp104 and Dicer as homeostatic controllers that buffer environmentally induced stochastic epigenetic variation and toxic aggregation of prionogenic proteins.

Annotation

GO biological process

GO:0071218 - cellular response to misfolded protein

Genes:

GO:0033562 - co-transcriptional gene silencing by RNA interference machinery

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GO:0042026 - protein refolding

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GO cellular component

GO:0005737 - cytoplasm

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GO:0005634 - nucleus

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GO:0000932 - P-body

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GO molecular function

GO:0140545 - ATP-dependent protein disaggregase activity

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Single locus phenotype

FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

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Genotypes:

FYPO:0004809 - decreased duration of heterochromatin maintenance involved in chromatin silencing at centromere outer repeat

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Genotypes:

FYPO:0000888 - decreased histone H3-K9 dimethylation at centromere outer repeat during vegetative growth

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FYPO:0004810 - decreased protein localization to nucleus, with protein mislocalized to cytoplasmic foci

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FYPO:0004808 - increased cellular protein aggregate level during cellular response to heat

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Genotypes:

FYPO:0000220 - increased centromeric outer repeat transcript level

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Genotypes:

FYPO:0002664 - increased level of stress responsive gene mRNA during vegetative growth

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Genotypes:

FYPO:0000825 - increased RNA level during vegetative growth

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Genotypes:

FYPO:0000228 - lagging mitotic chromosomes

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