The intron in centromeric noncoding RNA facilitates RNAi-mediated formation of heterochromatin

Autor: Tatsuhiro Yumikake, Kojiro Ishii, Madoka Chinen, Takashi Ideue, Misuzu Sakamoto, Kohei Dohke, Jun-ichi Nakayama, Misato Morita, Chihiro Tsukahara, Masatoshi Mutazono, Tokio Tani, Shiori Nishioka
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
RNA
Untranslated
Euchromatin
RNA splicing
Exonic splicing enhancer
Gene Expression
Yeast and Fungal Models
Biochemistry
Schizosaccharomyces Pombe
RNA interference
Heterochromatin
Small interfering RNAs
Genetics (clinical)
Genetics
Centromeres
Chromosome Biology
Polynucleotide Adenylyltransferase
Genomics
464.27
Chromatin
Nucleic acids
Genetic interference
Experimental Organism Systems
Epigenetics
RNA Splicing Factors
Research Article
Chromosome Structure and Function
lcsh:QH426-470
Centromere
Biology
Genome Complexity
Research and Analysis Methods
Methylation
Chromosomes
03 medical and health sciences
Splicing factor
Model Organisms
Schizosaccharomyces
Non-coding RNA
Molecular Biology
Ecology
Evolution
Behavior and Systematics
Intron
Organisms
Fungi
Biology and Life Sciences
Computational Biology
Cell Biology
Introns
Yeast
Gene regulation
lcsh:Genetics
030104 developmental biology
RNA processing
RNA
Zdroj: PLoS Genetics, Vol 13, Iss 2, p e1006606 (2017)
PLoS Genetics
ISSN: 1553-7404
1553-7390
Popis: In fission yeast, the formation of centromeric heterochromatin is induced through the RNA interference (RNAi)-mediated pathway. Some pre-mRNA splicing mutants (prp) exhibit defective formation of centromeric heterochromatin, suggesting that splicing factors play roles in the formation of heterochromatin, or alternatively that the defect is caused by impaired splicing of pre-mRNAs encoding RNAi factors. Herein, we demonstrate that the splicing factor spPrp16p is enriched at the centromere, and associates with Cid12p (a factor in the RNAi pathway) and the intron-containing dg ncRNA. Interestingly, removal of the dg intron, mutations of its splice sites, or replacement of the dg intron with an euchromatic intron significantly decreased H3K9 dimethylation. We also revealed that splicing of dg ncRNA is repressed in cells and its repression depends on the distance from the transcription start site to the intron. Inefficient splicing was also observed in other intron-containing centromeric ncRNAs, dh and antisense dg, and splicing of antisense dg ncRNA was repressed in the presence of the RNAi factors. Our results suggest that the introns retained in centromeric ncRNAs work as facilitators, co-operating with splicing factors assembled on the intron and serving as a platform for the recruitment of RNAi factors, in the formation of centromeric heterochromatin.
Author summary Formation of centromeric heterochromatin is required for correct segregation of sister chromatids during mitosis. In fission yeast, formation of heterochromatin at centromeres is performed through the RNA interference (RNAi) system, which involves processing of noncoding RNAs transcribed from the centromeres. We found that the intron in the centromeric dg ncRNAs facilitates formation of centromeric heterochromatin in fission yeast. We showed that the splicing factor spPrp16p associates with the RNAi factor and intron-containing dg ncRNA. Removal of or mutations in the dg intron significantly decreased H3K9 dimethylation, suggesting that the intron and associated splicing factors serve as a platform for recruitment of RNAi factors. Inefficient splicing is a hallmark of intron-containing centromeric ncRNAs. Such repression of splicing seems to be important for facilitation of heterochromatin formation. Introns in euchromatic regions are removed by splicing to generate functional RNAs, whereas centromeric introns are retained in ncRNAs by splicing repression and play roles in gene silencing. Our findings shed light on the novel roles of introns in epigenetic regulation of gene expression and heterochromatin formation.
Databáze: OpenAIRE
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