6月3日，Nature Structural & Molecular Biology雜志報道了內(nèi)含子RNA調(diào)節(jié)組蛋白賴氨酸N端甲基轉(zhuǎn)移酶EZH2表觀遺傳調(diào)控的最新進(jìn)展,。
在基因組許多位點(diǎn)的表觀遺傳修飾異常是腫瘤的一個重要特征。有觀點(diǎn)認(rèn)為,，某些RNA分子可指導(dǎo)抑制性多梳蛋白復(fù)合物（PRC2）到達(dá)特定的染色質(zhì)區(qū)域,。
研究者利用體內(nèi)交叉連接手段在腫瘤細(xì)胞中檢測和確定PRC2-RNA直接相互作用，發(fā)現(xiàn)了許多能結(jié)合組蛋白賴氨酸N端甲基轉(zhuǎn)移酶EZH2核心成分的內(nèi)含子RNA序列,。這些序列可調(diào)節(jié)基因組中EZH2序列的轉(zhuǎn)錄產(chǎn)出,。H3K4甲基轉(zhuǎn)移酶基因SMYD3具有EZH2結(jié)合的內(nèi)含子RNA,。該內(nèi)含子RNA的過表達(dá)伴有EZH2在其相應(yīng)基因組片段上結(jié)合的增加。該內(nèi)含子RNA的過表達(dá)足以降低內(nèi)源轉(zhuǎn)錄物及蛋白的減少,，導(dǎo)致培養(yǎng)細(xì)胞和動物模型的生長能力的降低,。
這些發(fā)現(xiàn)表明，內(nèi)含子RNA在轉(zhuǎn)錄水平精細(xì)調(diào)節(jié)基因表達(dá)中發(fā)揮重要作用,。（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.
