Defects in RNA quality control factors reveal RNAi-independent nucleation of heterochromatin

Nat Struct Mol Biol. 2011 Sep 4;18(10):1132-8. doi: 10.1038/nsmb.2122.

Abstract

Heterochromatin assembly at Schizosaccharomyces pombe centromeres involves a self-reinforcing loop mechanism wherein chromatin-bound RNAi factors facilitate targeting of Clr4-Rik1 methyltransferase. However, the initial nucleation of heterochromatin has remained elusive. We show that cells lacking Mlo3, a protein involved in mRNP biogenesis and RNA quality control, assemble functional heterochromatin in RNAi-deficient cells. Heterochromatin restoration is linked to RNA surveillance because loss of Mlo3-associated TRAMP also rescues heterochromatin defects of RNAi mutants. mlo3Δ, which causes accumulation of bidirectional repeat-transcripts, restores Rik1 enrichment at repeats and triggers de novo heterochromatin formation in the absence of RNAi. RNAi-independent heterochromatin nucleation occurs at selected euchromatic loci that show upregulation of antisense RNAs in mlo3Δ cells. We find that the exosome RNA degradation machinery acts parallel to RNAi to promote heterochromatin formation at centromeres. These results suggest that RNAi-independent mechanisms exploit transcription and non-coding RNAs to nucleate heterochromatin.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Centromere
  • Heterochromatin / chemistry*
  • Heterochromatin / genetics
  • Mutation
  • Quality Control*
  • RNA Interference*
  • Schizosaccharomyces / genetics

Substances

  • Heterochromatin