Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA.

Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA.
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DOI:
10.1016/j.molcel.2014.12.017
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发表时间:
2015-02-05
期刊:
影响因子:
16
通讯作者:
Cech, Thomas R.
Cech, Thomas R.
中科院分区:
生物学1区
文献类型:
--
作者:
Davidovich, Chen;Wang, Xueyin;Cifuentes-Rojas, Catherine;Goodrich, Karen J.;Gooding, Anne R.;Lee, Jeannie T.;Cech, Thomas R.

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Polycomb repressive complex-2(PRC 2)是一种组蛋白甲基转移酶,在发育和癌症过程中表观遗传沉默所需。早期的工作表明PRC 2与某些长的非编码RNA的结合特异性,用于招募到染色质。最近的研究提供了支持和反对这一观点的证据。在这里,我们桥接了PRC 2-RNA相互作用的两个现有模型。RepA RNA是PRC 2的良好结合伴侣,而多种非相关RNA(包括细菌mRNA)也结合PRC 2; Kd在一定程度上取决于实验条件。人和小鼠PRC 2在体外具有广泛相似的RNA结合特性。通过细胞中明确定义的RNA基序对支持PRC 2位点特异性募集的现有模型的证据进行检查,结果显示结果是PRC 2独立的。我们的结论是,混杂和特异性的PRC 2在体外的RNA结合活性是不相互排斥的,在体内的结合特异性仍有待证明。
Polycomb repressive complex-2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Early works suggested binding specificity of PRC2 to certain long non-coding RNAs for recruitment to chromatin. More recent studies provided evidence both in favor and against this idea. Here, we bridge the two existing models of PRC2-RNA interaction. RepA RNA is a good binding partner for PRC2, while multiple non-relevant RNAs, including bacterial mRNAs, also bind PRC2; with Kd's depend to some extent on the experimental conditions. Human and mouse PRC2 have broadly similar RNA-binding properties in vitro. Examination of evidence supporting an existing model for site-specific recruitment of PRC2 by a well-defined RNA motif in cells reveals that results are PRC2-independent. We conclude that promiscuous and specific RNA-binding activities of PRC2 in vitro are not mutually exclusive, and that binding specificity in vivo remains to be demonstrated.
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