Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
RNA. 2013 Apr;19(4):429-42. doi: 10.1261/rna.037598.112. Epub 2013 Feb 19.
A plethora of noncoding (nc) RNAs has been revealed through the application of high-throughput analysis of the transcriptome, and this has led to an intensive search for possible biological functions attributable to these transcripts. A major category of functional ncRNAs that has emerged is for those that are implicated in coordinate gene silencing, either in cis or in trans. The archetype for this class is the well-studied long ncRNA Xist which functions in cis to bring about transcriptional silencing of an entire X chromosome in female mammals. An important step in X chromosome inactivation is the recruitment of the Polycomb repressive complex PRC2 that mediates histone H3 lysine 27 methylation, a hallmark of the inactive X chromosome, and recent studies have suggested that this occurs as a consequence of PRC2 interacting directly with Xist RNA. Accordingly, other ncRNAs have been linked to PRC2 targeting either in cis or in trans, and here also the mechanism has been proposed to involve direct interaction between PRC2 proteins and the different ncRNAs. In this review, I discuss the evidence for and against this hypothesis, in the process highlighting alternative models and discussing experiments that, in the future, will help to resolve existing discrepancies.
通过对转录组进行高通量分析，揭示了大量的非编码（nc）RNA，这促使人们对这些转录本可能具有的生物学功能进行了深入研究。功能 ncRNA 的一个主要类别是那些涉及协调基因沉默的 ncRNA，无论是顺式作用还是反式作用。这一类的典型代表是研究得很好的长 ncRNA Xist，它在顺式作用中导致雌性哺乳动物整个 X 染色体的转录沉默。X 染色体失活的一个重要步骤是募集多梳抑制复合物 PRC2，该复合物介导组蛋白 H3 赖氨酸 27 甲基化，这是失活 X 染色体的标志，最近的研究表明，这是 PRC2 与 Xist RNA 直接相互作用的结果。因此，其他 ncRNA 已被链接到 PRC2 的顺式或反式靶向，并且在这里也提出了该机制涉及 PRC2 蛋白与不同 ncRNA 之间的直接相互作用的假说。在这篇综述中，我讨论了支持和反对这一假设的证据，同时强调了替代模型，并讨论了未来有助于解决现有差异的实验。
