Portoso Manuela, Ragazzini Roberta, Brenčič Živa, Moiani Arianna, Michaud Audrey, Vassilev Ivaylo, Wassef Michel, Servant Nicolas, Sargueil Bruno, Margueron Raphaël
Institut Curie, PSL Research University, Paris, France.
INSERM U934, CNRS UMR3215, Paris, France.
EMBO J. 2017 Apr 13;36(8):981-994. doi: 10.15252/embj.201695335. Epub 2017 Feb 6.
Long non-coding RNAs (lncRNAs) play diverse roles in physiological and pathological processes. Several lncRNAs have been suggested to modulate gene expression by guiding chromatin-modifying complexes to specific sites in the genome. However, besides the example of Xist, clear-cut evidence demonstrating this novel mode of regulation remains sparse. Here, we focus on , a lncRNA that is overexpressed in several tumor types and previously proposed to play a key role in gene silencing through direct recruitment of Polycomb Repressive Complex 2 (PRC2) to defined genomic loci. Using genetic tools and a novel RNA-tethering system, we investigated the interplay between and PRC2 in gene silencing. Surprisingly, we observed that forced overexpression of in breast cancer cells leads to subtle transcriptomic changes that appear to be independent of PRC2. Mechanistically, we found that artificial tethering of to chromatin causes transcriptional repression, but that this effect does not require PRC2. Instead, PRC2 recruitment appears to be a consequence of gene silencing. We propose that PRC2 binding to RNA might serve functions other than chromatin targeting.
长链非编码RNA（lncRNAs）在生理和病理过程中发挥着多种作用。已有研究表明，一些lncRNAs可通过引导染色质修饰复合物至基因组中的特定位点来调节基因表达。然而，除了Xist这个例子外，证明这种新型调控模式的明确证据仍然稀少。在这里，我们聚焦于[具体lncRNA名称未给出]，一种在多种肿瘤类型中过表达的lncRNA，此前有研究提出它通过将多梳抑制复合物2（PRC2）直接招募至特定基因组位点在基因沉默中发挥关键作用。利用遗传学工具和一种新型的RNA拴系系统，我们研究了[具体lncRNA名称未给出]与PRC2在基因沉默中的相互作用。令人惊讶的是，我们观察到在乳腺癌细胞中强制过表达[具体lncRNA名称未给出]会导致细微的转录组变化，这些变化似乎与PRC2无关。从机制上讲，我们发现将[具体lncRNA名称未给出]人工拴系至染色质会导致转录抑制，但这种效应并不需要PRC2。相反，PRC2的招募似乎是基因沉默的结果。我们提出PRC2与RNA的结合可能具有除染色质靶向之外的其他功能。
