Fission yeast Caprin protein is required for efficient heterochromatin establishment

March 2025, Bayne Lab, PLOS Genetics

Authors

Zhang, H., Kapitonova, E., Orrego, A., Spanos, C., Strachan, J., and Bayne, E.H.

Summary

By Dipika Mishra, Akiyoshi Lab

Heterochromatin, or the ‘dark matter’ of the genome, plays a critical role in the maintenance of genome integrity and in regulation of gene expression. This dense region of the genome is characterised by a distinct pattern of chromatin modifications including histone hypo-acetylation and hypermethylation of lysine 9 of histone H3. Although previous studies have identified the mechanisms associated with the maintenance of pre-existing heterochromatin, the process of establishment of new heterochromatin is not well understood. 

To explore the molecular mechanisms underlying heterochromatin establishment in S. pombe, researchers in the Bayne lab developed a novel assay involving genetic abolition and re-establishment of heterochromatin. By using this assay to screen candidate deletion mutants, they identified a novel factor named Cpn1 to be essential for efficient heterochromatin establishment.  Cpn1 is orthologous to human RNA binding protein CAPRIN1, and the researchers found that, similar to its human counterpart, Cpn1 also associates with cytoplasmic stress granules during stress. Furthermore, they uncovered evidence of interplay between heterochromatin integrity and ribonucleoprotein granule formation, and identified a specific role for Cpn1 in supporting heterochromatin establishment by facilitating removal of excessive heterochromatic transcripts. This study thus unlocks a new connection between RNA homeostasis and heterochromatin assembly.

Bayne image March 2025
We discovered that Caprin protein (Cpn1) promotes assembly of heterochromatin at centromeres by facilitating removal of excess centromeric transcripts. The figure shows that centromeric (cen(dg)) transcripts over-accumulate at centromeres in the absence of Cpn1, and also accumulate in the cytoplasm in a Cpn1-dependent manner in the absence of the nuclease Dhp1, suggesting that Cpn1 helps target these transcripts for degradation in the cytoplasm.

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