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The Proper Splicing of RNAi Factors Is Critical for Pericentric Heterochromatin Assembly in Fission Yeast


Heterochromatin formation at specific genomic regions is critical for processes as diverse as gene expression and chromosome segregation. The formation of silent heterochromatin at repetitive DNA elements requires processing of transcripts by the RNA interference machinery. Curiously, factors involved in proper RNA splicing are required for heterochromatin assembly, and it was proposed that splicing factors provide a platform for the recruitment of RNAi complexes independently of their role in regulating splicing. In this study, we found several novel splicing factors involved in heterochromatin assembly. Our analysis of genome-wide splicing patterns by RNA sequencing showed that the mRNAs of RNAi factors are very sensitive to perturbations of RNA splicing machinery. Moreover, we found that splicing factors are critical for the production of a telomere shelterin component and proper telomeric heterochromatin assembly. Most importantly, we showed that introducing the cDNA versions of RNAi and shelterin components alleviates heterochromatin defects associated with splicing factor mutations. Thus splicing factors are required for heterochromatin assembly mainly by regulating the proper splicing of heterochromatin assembly factors.


Vyšlo v časopise: The Proper Splicing of RNAi Factors Is Critical for Pericentric Heterochromatin Assembly in Fission Yeast. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004334
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004334

Souhrn

Heterochromatin formation at specific genomic regions is critical for processes as diverse as gene expression and chromosome segregation. The formation of silent heterochromatin at repetitive DNA elements requires processing of transcripts by the RNA interference machinery. Curiously, factors involved in proper RNA splicing are required for heterochromatin assembly, and it was proposed that splicing factors provide a platform for the recruitment of RNAi complexes independently of their role in regulating splicing. In this study, we found several novel splicing factors involved in heterochromatin assembly. Our analysis of genome-wide splicing patterns by RNA sequencing showed that the mRNAs of RNAi factors are very sensitive to perturbations of RNA splicing machinery. Moreover, we found that splicing factors are critical for the production of a telomere shelterin component and proper telomeric heterochromatin assembly. Most importantly, we showed that introducing the cDNA versions of RNAi and shelterin components alleviates heterochromatin defects associated with splicing factor mutations. Thus splicing factors are required for heterochromatin assembly mainly by regulating the proper splicing of heterochromatin assembly factors.


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