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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失调。

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

作者信息

Poltronieri Palmiro

机构信息

Agrofood Department, National Research Council, CNR-ISPA, 73100 Lecce, Italy.

出版信息

Explor Target Antitumor Ther. 2024;5(4):841-876. doi: 10.37349/etat.2024.00252. Epub 2024 Jul 22.

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.

摘要

最近,非编码RNA(ncRNA)与表观遗传机制之间的相互作用有了新的数据补充。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、抑制状态和转录中活跃状态的潜在机制。主要关注点是作为组装蛋白质复合物支架的长链非编码RNA(lncRNA)。本综述不涉及RNA在充当微小RNA海绵或诱饵功能方面的作用。一些lncRNA被证明可通过与多梳抑制复合物和混合谱系白血病(MLL)激活复合物相互作用来调节染色质的激活和抑制。多个研究团队报道了zeste同源物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癌症治疗新疗法开辟了前景。最后,lncRNA与癌症中表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节表转录组调控RNA的前景可能会带来新的化合物用于各类癌症的治疗。

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