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Reference - PMID:20018856 - Involvement of the spliceosomal U4 small nuclear RNA in heterochromatic gene silencing at fission yeast centromeres.

Reference summary

PubMed ID
PMID:20018856
Title
Involvement of the spliceosomal U4 small nuclear RNA in heterochromatic gene silencing at fission yeast centromeres.
Authors
Chinen M, Morita M, Fukumura K, Tani T
Citation
J Biol Chem 2010 Feb 19;285(8):5630-8
Publication year
2010
Abstract
prp13-1 is one of the mutants isolated in a screen for defective pre-mRNA splicing at a nonpermissive temperature in fission yeast Schizosaccharomyces pombe. We cloned the prp13(+) gene and found that it encodes U4 small nuclear RNA (snRNA) involved in the assembly of the spliceosome. The prp13-1 mutant produced elongated cells, a phenotype similar to cell division cycle mutants, and displays a high incidence of lagging chromosomes on anaphase spindles. The mutant is hypersensitive to the microtubule-destabilizing drug thiabendazole, supporting that prp13-1 has a defect in chromosomal segregation. We found that the prp13-1 mutation resulted in expression of the ura4(+) gene inserted in the pericentromeric heterochromatin region and reduced recruitment of the heterochromatin protein Swi6p to that region, indicating defects in the formation of pericentromeric heterochromatin, which is essential for the segregation of chromosomes, in prp13-1. The formation of centromeric heterochromatin is induced by the RNA interference (RNAi) system in S. pombe. In prp13-1, the processing of centromeric noncoding RNAs to siRNAs, which direct the heterochromatin formation, was impaired and unprocessed noncoding RNAs were accumulated. These results suggest that U4 snRNA is required for the RNAi-directed heterochromatic gene silencing at the centromeres. In relation to the linkage between the spliceosomal U4 snRNA and the RNAi-directed formation of heterochromatin, we identified a mRNA-type intron in the centromeric noncoding RNAs. We propose a model in which the assembly of the spliceosome or a sub-spliceosome complex on the intron-containing centromeric noncoding RNAs facilitates the RNAi-directed formation of heterochromatin at centromeres, through interaction with the RNA-directed RNA polymerase complex.

Annotation

GO biological process

GO:0045292 - mRNA cis splicing, via spliceosome

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Multi-locus phenotype

FYPO:0004742 - normal chromatin silencing at centromere outer repeat

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Single locus phenotype

FYPO:0002346 - abnormal chromatin silencing at centromere outer repeat

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FYPO:0003681 - decreased protein level at centromere outer repeat heterochromatin

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FYPO:0001645 - decreased protein-protein interaction

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FYPO:0000220 - increased centromeric outer repeat transcript level

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FYPO:0001908 - increased pre-mRNA level

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FYPO:0002061 - inviable vegetative cell population

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FYPO:0000228 - lagging mitotic chromosomes

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FYPO:0003620 - normal pre-mRNA level

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FYPO:0000091 - sensitive to thiabendazole

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FYPO:0002060 - viable vegetative cell population

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