Davidovich Chen, Wang Xueyin, Cifuentes-Rojas Catherine, Goodrich Karen J, Gooding Anne R, Lee Jeannie T, Cech Thomas R
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Mol Cell. 2015 Feb 5;57(3):552-8. doi: 10.1016/j.molcel.2014.12.017. Epub 2015 Jan 15.
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; Kds 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.
多梳抑制复合物2（PRC2）是一种组蛋白甲基转移酶，在发育和癌症过程中的表观遗传沉默中发挥作用。早期研究表明PRC2对某些长链非编码RNA具有结合特异性，以便招募至染色质。最近的研究则提供了支持和反对这一观点的证据。在此，我们弥合了PRC2与RNA相互作用的两种现有模型。RepA RNA是PRC2的良好结合伴侣，而包括细菌mRNA在内的多种不相关RNA也能与PRC2结合；解离常数在一定程度上取决于实验条件。人和小鼠的PRC2在体外具有广泛相似的RNA结合特性。对支持细胞中通过明确的RNA基序对PRC2进行位点特异性招募的现有模型的证据进行研究发现，结果与PRC2无关。我们得出结论，PRC2在体外的混杂和特异性RNA结合活性并非相互排斥，而其在体内的结合特异性仍有待证明。
