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Fission yeast Caprin protein is required for efficient heterochromatin establishment
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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.
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Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Heterochromatin: Guardian of the Genome
Janssen, A., Colmenares, S. U., & Karpen, G. H. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062653 · Cited by 500
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Metadata
- Authors
- Zhang, H., Kapitonova, E., Orrego, A., Spanos, C., Strachan, J., & Bayne, E. H.
- Affiliations
- University of Edinburgh (GB)
- Corresponding author
- Bayne, Elizabeth H.
- Venue
- PLOS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2025-03-10
- Volume
- 21
- Issue
- 3
- Pages
- e1011620
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC11918387
- OpenAlex
- W4408281078
- Cited by
- 1
- References
- 3
- Citations by year
- 2025: 1
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Update notices
- new_version (2025-03-18)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wellcome Trust (202771/Z/16/Z)
- Darwin Trust of Edinburgh
- University of Edinburgh
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- Schizosaccharomyces pombe, stress granules, ribonucleoprotein granules, centromere, RNA-binding proteins, histone methylation, non-coding RNA
- MeSH terms
- Stress Granules, Centromere, Heterochromatin, Histones, Humans, Ribonucleoproteins, Schizosaccharomyces, Gene Expression Regulation, Fungal, RNA-Binding Proteins, Schizosaccharomyces pombe Proteins
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