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长非编码 RNA 对 polycomb 抑制复合物的调控。

The control of polycomb repressive complexes by long noncoding RNAs.

机构信息

Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Curriculum in Mechanistic, Interdisciplinary Studies of Biological Systems, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

出版信息

Wiley Interdiscip Rev RNA. 2021 Nov;12(6):e1657. doi: 10.1002/wrna.1657. Epub 2021 Apr 16.

Abstract

The polycomb repressive complexes 1 and 2 (PRCs; PRC1 and PRC2) are conserved histone-modifying enzymes that often function cooperatively to repress gene expression. The PRCs are regulated by long noncoding RNAs (lncRNAs) in complex ways. On the one hand, specific lncRNAs cause the PRCs to engage with chromatin and repress gene expression over genomic regions that can span megabases. On the other hand, the PRCs bind RNA with seemingly little sequence specificity, and at least in the case of PRC2, direct RNA-binding has the effect of inhibiting the enzyme. Thus, some RNAs appear to promote PRC activity, while others may inhibit it. The reasons behind this apparent dichotomy are unclear. The most potent PRC-activating lncRNAs associate with chromatin and are predominantly unspliced or harbor unusually long exons. Emerging data imply that these lncRNAs promote PRC activity through internal RNA sequence elements that arise and disappear rapidly in evolutionary time. These sequence elements may function by interacting with common subsets of RNA-binding proteins that recruit or stabilize PRCs on chromatin. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

摘要

多梳抑制复合物 1 和 2(PRC;PRC1 和 PRC2)是保守的组蛋白修饰酶,通常协同作用以抑制基因表达。PRC 受到长非编码 RNA(lncRNA)的复杂调节。一方面,特定的 lncRNA 导致 PRC 与染色质结合,并在可以跨越兆碱基的基因组区域上抑制基因表达。另一方面,PRC 以似乎没有序列特异性的方式结合 RNA,至少在 PRC2 的情况下,直接 RNA 结合会抑制酶的活性。因此,一些 RNA 似乎促进 PRC 活性,而另一些则可能抑制它。这种明显的二分法的原因尚不清楚。最有效的 PRC 激活 lncRNA 与染色质结合,主要是未剪接的或具有异常长的外显子。新出现的数据表明,这些 lncRNA 通过在进化过程中迅速出现和消失的内部 RNA 序列元件来促进 PRC 活性。这些序列元件可能通过与招募或稳定 PRC 于染色质上的常见 RNA 结合蛋白子集相互作用来发挥作用。本文属于以下类别:RNA 与蛋白质和其他分子的相互作用 > 蛋白-RNA 识别 RNA 与蛋白质和其他分子的相互作用 > RNA-蛋白质复合物 RNA 与蛋白质和其他分子的相互作用 > 蛋白-RNA 相互作用:功能意义。

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