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PMID:25543137

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Citation

Oberti, D, Biasini, A, Kirschmann, MA, Genoud, C, Stunnenberg, R, Shimada, Y and Bühler, M (2015) Dicer and Hsp104 function in a negative feedback loop to confer robustness to environmental stress. Cell Rep 10:47-61

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.

Links

PubMed Online version:10.1016/j.celrep.2014.12.006

Keywords

Environment; Epigenesis, Genetic; Feedback, Physiological; Heat-Shock Proteins/genetics; Heat-Shock Proteins/metabolism; Phenotype; Prions/genetics; Ribonuclease III/genetics; Ribonuclease III/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Stress, Physiological/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

SCHPO:DCP2

part_of

GO:0000932: P-body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:HS104

involved_in

GO:0071218: cellular response to misfolded protein

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(PomBase:SPCC188.13c)

Seeded From UniProt

complete

SCHPO:HS104

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:HS104

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:HS104

involved_in

GO:0042026: protein refolding

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(PomBase:SPCC188.13c)

Seeded From UniProt

complete

SCHPO:DCR1

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:DCR1

involved_in

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

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(PomBase:SPBC16D10.08c)

Seeded From UniProt

complete

SCHPO:PABP

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:DCR1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:DCR1

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

exists_during:(GO:0034605)

Seeded From UniProt

complete

SCHPO:DCR1

involved_in

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

ECO:0000315: mutant phenotype evidence used in manual assertion

P

has_regulation_target:(PomBase:SPBC16D10.08c)

Seeded From UniProt

complete

Notes

See also

References

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