Brönner Cornelia, Salvi Luca, Zocco Manuel, Ugolini Ilaria, Halic Mario
Department of Biochemistry, Gene Center, University of Munich (LMU), 81377 Munich, Germany.
Genome Res. 2017 Jul;27(7):1174-1183. doi: 10.1101/gr.216986.116. Epub 2017 Apr 12.
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 in that 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 distant reporter 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.
长链非编码RNA（lncRNAs）在调控基因表达、染色质动态变化和细胞分化中发挥着保守作用。在许多真核生物中，它们作为RNA干扰（RNAi）介导的异染色质形成或DNA甲基化的平台。我们发现，在没有RNA降解的情况下，转录区域的异染色质会丢失。我们表明，异染色质RNA保留在染色质上，形成DNA:RNA杂交体，并且需要被Ccr4-Not复合物或RNAi降解以维持异染色质沉默。Ccr4-Not复合物独立于H3K9me定位于染色质，并降解与染色质相关的转录本，这是转录沉默所必需的。在野生型细胞中，异染色质RNA而非常染色质RNA的过表达会导致染色质定位以及远处报告基因沉默的丧失。我们的结果表明，与染色质结合的RNA会破坏异染色质组织，并且在异染色质形成过程中需要被降解。
