4.8 Article

Splicing factors facilitate RNAi-directed silencing in fission yeast

Journal

SCIENCE
Volume 322, Issue 5901, Pages 602-606

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1164029

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Funding

  1. Epigenome Network of Excellence [EC-FP6/Contract/LSHG-CT2004-503433]
  2. UK Medical Research Council [G0301153/ID:69173]
  3. Wellcome Trust Prize Studentship [067844]
  4. Marie Curie Excellence Grant [MEXT-CT-014171]
  5. Wellcome Trust Principal Research Fellowship [065061/Z]
  6. MRC [G0301153] Funding Source: UKRI
  7. Medical Research Council [G0301153] Funding Source: researchfish

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Heterochromatin formation at fission yeast centromeres is directed by RNA interference (RNAi). Noncoding transcripts derived from centromeric repeats are processed into small interfering RNAs (siRNAs) that direct the RNA-induced transcriptional silencing (RITS) effector complex to engage centromer transcripts, resulting in recruitment of the histone H3 lysine 9 methyltransferase Clr4, and hence silencing. We have found that defects in specific splicing factors, but not splicing itself, affect the generation of centromeric siRNAs and consequently centromeric heterochromatin integrity. Moreover, splicing factors physically associate with Cid12, a component of the RNAi machinery, and with centromeric chromatin, consistent with a direct role in RNAi. We propose that spliceosomal complexes provide a platform for siRNA generation and hence facilitate effective centromere repeat silencing.

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