saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription.
saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription.
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DOI：
10.1038/cr.2016.22
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发表时间：
2016-03
期刊：
影响因子：
44.1
通讯作者：
Li LC
中科院分区：
文献类型：
--
作者：
Portnoy V;Lin SH;Li KH;Burlingame A;Hu ZH;Li H;Li LC
靶向特定启动子区域的小激活RNA（saRNA）能够在转录水平上刺激基因表达，这种现象称为RNA激活（RNAa）。已知RNAa依赖于Ago 2并且与靶启动子处的表观遗传变化相关。然而，RNAa的精确分子机制仍然难以捉摸。使用人CDKN 1A（p21）作为模型基因，我们表征了RNAa的分子性质。我们发现，saRNA引导Ago 2与靶启动子结合。加载saRNA的Ago 2促进RNA诱导的转录激活（RITA）复合物的组装，除了saRNA-Ago 2复合物之外，RITA复合物还包括RHA和CTR 9，后者是PAF 1复合物的组分。RITA与RNA聚合酶II相互作用以刺激转录起始和生产性延伸，伴随着组蛋白2B的monoubiquitination。我们的研究结果建立了一个细胞RNA引导的基因组靶向和转录激活机制的存在，并提供了重要的新的机制见解RNAa过程。
Small activating RNAs (saRNAs) targeting specific promoter regions are able to stimulate gene expression at the transcriptional level, a phenomenon known as RNA activation (RNAa). It is known that RNAa depends on Ago2 and is associated with epigenetic changes at the target promoters. However, the precise molecular mechanism of RNAa remains elusive. Using human CDKN1A (p21) as a model gene, we characterized the molecular nature of RNAa. We show that saRNAs guide Ago2 to and associate with target promoters. saRNA-loaded Ago2 facilitates the assembly of an RNA-induced transcriptional activation (RITA) complex, which, in addition to saRNA-Ago2 complex, includes RHA and CTR9, the latter being a component of the PAF1 complex. RITA interacts with RNA polymerase II to stimulate transcription initiation and productive elongation, accompanied by monoubiquitination of histone 2B. Our results establish the existence of a cellular RNA-guided genome-targeting and transcriptional activation mechanism and provide important new mechanistic insights into the RNAa process.