title: Accumulation of RNA on chromatin disrupts heterochromatic silencing.
abstract: Long noncoding RNAs (lncRNAs) play a conserved role in regulating gene expression, chromatin dynamics, and cell differentiation. They serve as a platform for RNA interference (RNAi)-mediated heterochromatin formation or DNA methylation in many eukaryotic organisms. We found inSchizosaccharomyces pombethat heterochromatin is lost at transcribed regions in the absence of RNA degradation. We show that heterochromatic RNAs are retained on chromatin, form DNA:RNA hybrids, and need to be degraded by the Ccr4-Not complex or RNAi to maintain heterochromatic silencing. The Ccr4-Not complex is localized to chromatin independently of H3K9me and degrades chromatin-associated transcripts, which is required for transcriptional silencing. Overexpression of heterochromatic RNA, but not euchromatic RNA, leads to chromatin localization and loss of silencing of a distantade6reporter in wild-type cells. Our results demonstrate that chromatin-bound RNAs disrupt heterochromatin organization and need to be degraded in a process of heterochromatin formation.
authors.affiliation: Department of Biochemistry, Gene Center, University of Munich (LMU), 81377 Munich, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Brönner
authors.affiliation: Department of Biochemistry, Gene Center, University of Munich (LMU), 81377 Munich, Germany.
authors.forename: Luca
authors.initials: L
authors.lastname: Salvi
authors.affiliation: Department of Biochemistry, Gene Center, University of Munich (LMU), 81377 Munich, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Zocco
authors.affiliation: Department of Biochemistry, Gene Center, University of Munich (LMU), 81377 Munich, Germany.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ugolini
authors.affiliation: Department of Biochemistry, Gene Center, University of Munich (LMU), 81377 Munich, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Halic
mesh_terms: D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C519160:Ccr4 protein, S pombe; D006570:Heterochromatin; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins