Regulatory RNAs: role as scaffolds assembling protein complexes and their epigenetic deregulation

P. Poltronieri
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Abstract

Recently, new data have been added to the interaction between non-coding RNAs (ncRNAs) and epigenetic machinery. Epigenetics includes enzymes involved in DNA methylation, histone modifications, and RNA modifications, and mechanisms underlying chromatin structure, repressive states, and active states operating in transcription. The main focus is on long ncRNAs (lncRNAs) acting as scaffolds to assemble protein complexes. This review does not cover RNA’s role in sponging microRNAs, or decoy functions. Several lncRNAs were shown to regulate chromatin activation and repression by interacting with Polycomb repressive complexes and mixed-lineage leukemia (MLL) activating complexes. Various groups reported on enhancer of zeste homolog 2 (EZH2) interactions with regulatory RNAs. Knowledge of the function of these complexes opens the perspective to develop new therapeutics for cancer treatment. Lastly, the interplay between lncRNAs and epitranscriptomic modifications in cancers paves the way for new targets in cancer therapy. The approach to inhibit lncRNAs interaction with protein complexes and perspective to regulate epitrascriptomics-regulated RNAs may bring new compounds as therapeuticals in various types of cancer.
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调控 RNA:作为组装蛋白质复合物的支架的作用及其表观遗传学上的失调
最近,非编码 RNA(ncRNA)与表观遗传机制之间的相互作用又有了新的数据。表观遗传学包括参与 DNA 甲基化、组蛋白修饰和 RNA 修饰的酶,以及染色质结构、抑制状态和转录活动状态的内在机制。主要重点是作为组装蛋白质复合物支架的长 ncRNA(lncRNA)。本综述不包括 RNA 在微 RNA 中的作用或诱饵功能。研究表明,一些 lncRNA 可通过与多聚胞抑制复合体和混系白血病(MLL)激活复合体相互作用,调节染色质的激活和抑制。多个研究小组报告了泽斯特同源增强子 2(EZH2)与调控 RNA 的相互作用。对这些复合物功能的了解为开发治疗癌症的新疗法打开了视野。最后,lncRNA 与癌症表观转录组修饰之间的相互作用为癌症治疗的新靶点铺平了道路。抑制 lncRNA 与蛋白质复合物相互作用的方法以及调控表转录组调控的 RNA 的视角可能会为各种癌症的治疗带来新的化合物。
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