2024/06/19 by Haidao Zhang, Ekaterina Kapitonova, Adriana Orrego +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · Agricultural and Biological Sciences · #RNA and protein synthesis mechanisms #RNA Interference and Gene Delivery #Chromosomal and Genetic Variations
paper · pdf · doi:10.1101/2024.06.19.598224
openalex publication_date 2024/06/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
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, absence of Cpn1 leads to hyperaccumulation of centromeric 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.