Nat Struct Mol Biol:内含子RNA调节EZH2表观遗传调控

6月3日，Nature Structural & Molecular Biology杂志报道了内含子RNA调节组蛋白赖氨酸N端甲基转移酶EZH2表观遗传调控的最新进展。

在基因组许多位点的表观遗传修饰异常是肿瘤的一个重要特征。有观点认为，某些RNA分子可指导抑制性多梳蛋白复合物（PRC2）到达特定的染色质区域。

研究者利用体内交叉连接手段在肿瘤细胞中检测和确定PRC2-RNA直接相互作用，发现了许多能结合组蛋白赖氨酸N端甲基转移酶EZH2核心成分的内含子RNA序列。这些序列可调节基因组中EZH2序列的转录产出。H3K4甲基转移酶基因SMYD3具有EZH2结合的内含子RNA。该内含子RNA的过表达伴有EZH2在其相应基因组片段上结合的增加。该内含子RNA的过表达足以降低内源转录物及蛋白的减少，导致培养细胞和动物模型的生长能力的降低。

这些发现表明，内含子RNA在转录水平精细调节基因表达中发挥重要作用。（生物谷bioon.com)

doi:10.1016/j.cell.2011.10.017
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Intronic RNAs mediate EZH2 regulation of epigenetic targets

Sònia Guil,1 Marta Soler,1 Anna Portela,1 Jordi Carrère,1 Elena Fonalleras,1 Antonio Gómez,1 Alberto Villanueva2 & Manel Esteller1, 3,

Epigenetic deregulation at a number of genomic loci is one of the hallmarks of cancer. A role for some RNA molecules in guiding repressive polycomb complex PRC2 to specific chromatin regions has been proposed. Here we use an in vivo cross-linking method to detect and identify direct PRC2-RNA interactions in human cancer cells, revealing a number of intronic RNA sequences capable of binding to the core component EZH2 and regulating the transcriptional output of its genomic counterpart. Overexpression of EZH2-bound intronic RNA for the H3K4 methyltransferase gene SMYD3 is concomitant with an increase in EZH2 occupancy throughout the corresponding genomic fragment and is sufficient to reduce levels of the endogenous transcript and protein, resulting in reduced growth capability in cell culture and animal models. These findings reveal the role of intronic RNAs in fine-tuning gene expression regulation at the level of transcriptional control.