短串联连续鸟嘌呤重复序列靶向多梳抑制复合物 2 到 RNA。
Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines.
机构信息
Department of Chemistry & Biochemistry, BioFrontiers Institute and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder, CO 80309, USA.
Monash Bioinformatics Platform, Monash University, Clayton, VIC 3800, Australia; Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia.
出版信息
Mol Cell. 2017 Mar 16;65(6):1056-1067.e5. doi: 10.1016/j.molcel.2017.02.003.
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recognizes G > C,U ≫ A in single-stranded RNA and has a high affinity for folded guanine quadruplex (G4) structures but little binding to duplex RNAs. Importantly, G-tract motifs are significantly enriched among PRC2-binding transcripts in vivo. DNA sequences coding for PRC2-binding RNA motifs are enriched at PRC2-binding sites on chromatin and H3K27me3-modified nucleosomes. Collectively, the abundance of PRC2-binding RNA motifs rationalizes the promiscuous RNA binding of PRC2, and their enrichment at Polycomb target genes provides a means for RNA-mediated regulation.
多梳抑制复合物 2（PRC2）是一种组蛋白甲基转移酶，可将 H3K27 三甲基化，H3K27 是染色质被抑制的标志。哺乳动物 PRC2 随机结合 RNA，在体内有数千个靶转录本。但是 PRC2 在这些 RNA 中识别什么？在这里，我们表明纯化的人 PRC2 识别单链 RNA 中的 G > C，U ≫ A，并且对折叠的鸟嘌呤四链体（G4）结构具有高亲和力，但对双链 RNA 的结合能力较弱。重要的是，G 链段基序在体内 PRC2 结合的转录本中明显富集。编码 PRC2 结合 RNA 基序的 DNA 序列在染色质上的 PRC2 结合位点和 H3K27me3 修饰的核小体上富集。总之，PRC2 结合 RNA 基序的丰度合理地解释了 PRC2 随机结合 RNA 的现象，而它们在多梳靶基因中的富集为 RNA 介导的调控提供了一种手段。
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