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Reference - PMID:40063661 - Fission yeast Caprin protein is required for efficient heterochromatin establishment.

Reference summary

PubMed ID
PMID:40063661
Title
Fission yeast Caprin protein is required for efficient heterochromatin establishment.
Authors
Zhang H, Kapitonova E, Orrego A, Spanos C, Strachan J, Bayne EH
Citation
PLoS Genet 2025 Mar 10;21(3):e1011620
Publication year
2025
Abstract
Heterochromatin is a key feature of eukaryotic genomes that serves important regulatory and structural roles in regions such as centromeres. In fission yeast, maintenance of existing heterochromatic domains relies on positive feedback loops involving histone methylation and non-coding RNAs. However, requirements for de novo establishment of heterochromatin are less well understood. Here, through a cross-based assay we have identified a novel factor influencing the efficiency of heterochromatin establishment. We determine that the previously uncharacterised protein is an ortholog of human Caprin1, an RNA-binding protein linked to stress granule formation. We confirm that the fission yeast ortholog, here named Cpn1, also associates with stress granules, and we uncover evidence of interplay between heterochromatin integrity and ribonucleoprotein (RNP) granule formation, with heterochromatin mutants showing reduced granule formation in the presence of stress, but increased granule formation in the absence of stress. We link this to regulation of non-coding heterochromatic transcripts, since in heterochromatin-deficient cells, Cpn1 can be seen to colocalise with accumulating pericentromeric transcripts, and absence of Cpn1 leads to hyperaccumulation of these RNAs at centromeres. Together, our findings unveil a novel link between RNP homeostasis and heterochromatin assembly, and implicate Cpn1 and associated factors in facilitating efficient heterochromatin establishment by enabling removal of excess transcripts that would otherwise impair assembly processes.

Annotation

GO biological process

GO:0034063 - stress granule assembly

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GO cellular component

GO:0010494 - cytoplasmic stress granule

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Multi-locus phenotype

FYPO:0008415 - abnormal centromeric outer repeat transcript localization to the cytoplasm

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FYPO:0007224 - decreased heterochromatin assembly at centromere outer repeat during vegetative growth

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FYPO:0000220 - increased centromeric outer repeat transcript level

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FYPO:0007227 - increased number of R-loops at centromere

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FYPO:0007320 - increased stress granule assembly during vegetative growth

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FYPO:0002350 - normal stress granule assembly during vegetative growth

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Single locus phenotype

FYPO:0007223 - decreased establishment of chromatin silencing at centromere outer repeat region

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FYPO:0007224 - decreased heterochromatin assembly at centromere outer repeat during vegetative growth

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FYPO:0003101 - decreased heterochromatin assembly at protein coding gene

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FYPO:0001117 - decreased RNA level during vegetative growth

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FYPO:0007322 - decreased stress granule assembly during cellular response to heat

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FYPO:0000220 - increased centromeric outer repeat transcript level

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FYPO:0008413 - increased establishment of chromatin silencing at centromere outer repeat region

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FYPO:0007227 - increased number of R-loops at centromere

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FYPO:0001130 - increased protein localization to nucleus during vegetative growth

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FYPO:0000825 - increased RNA level during vegetative growth

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FYPO:0004749 - increased spatial extent of subtelomeric heterochromatin assembly

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FYPO:0007320 - increased stress granule assembly during vegetative growth

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FYPO:0007226 - normal chromatin silencing at heterochromatin island

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FYPO:0004744 - normal heterochromatin maintenance involved in chromatin silencing at centromere outer repeat

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FYPO:0004024 - normal protein localization to cytoplasmic stress granule

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FYPO:0007323 - normal stress granule assembly during cellular response to heat

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FYPO:0008414 - normal stress granule assembly during glucose starvation

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