Mangiavacchi Arianna, Morelli Gabriele, Orlando Valerio
BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Front Cell Dev Biol. 2023 Jan 25;11:1123975. doi: 10.3389/fcell.2023.1123975. eCollection 2023.
Non-coding DNA accounts for approximately 98.5% of the human genome. Once labeled as "junk DNA", this portion of the genome has undergone a progressive re-evaluation and it is now clear that some of its transcriptional products, belonging to the non-coding RNAs (ncRNAs), are key players in cell regulatory networks. A growing body of evidence demonstrates the crucial impact of regulatory ncRNAs on mammalian gene expression. Here, we focus on the defined relationship between chromatin-interacting RNAs, particularly long non-coding RNA (lncRNA), enhancer RNA (eRNA), non-coding natural antisense transcript (ncNAT), and circular RNA (circRNA) and epigenome, a common ground where both protein and RNA species converge to regulate cellular functions. Through several examples, this review provides an overview of the variety of targets, interactors, and mechanisms involved in the RNA-mediated modulation of loci-specific epigenetic states, a fundamental evolutive strategy to orchestrate mammalian gene expression in a timely and reversible manner. We will discuss how RNA-mediated epigenetic regulation impacts development and tissue homeostasis and how its alteration contributes to the onset and progression of many different human diseases, particularly cancer.
非编码DNA约占人类基因组的98.5%。这部分基因组曾被标记为“垃圾DNA”，但如今已逐渐得到重新评估，现在很清楚的是，其一些转录产物，即属于非编码RNA（ncRNAs）的部分，是细胞调控网络中的关键参与者。越来越多的证据表明调控性ncRNAs对哺乳动物基因表达具有至关重要的影响。在此，我们聚焦于染色质相互作用RNA之间明确的关系，特别是长链非编码RNA（lncRNA）、增强子RNA（eRNA）、非编码天然反义转录本（ncNAT）和环状RNA（circRNA）与表观基因组之间的关系，表观基因组是蛋白质和RNA物种共同汇聚以调节细胞功能的一个共同基础。通过几个例子，本综述概述了RNA介导的基因座特异性表观遗传状态调节所涉及的各种靶标、相互作用分子和机制，这是一种以及时且可逆的方式协调哺乳动物基因表达的基本进化策略。我们将讨论RNA介导的表观遗传调控如何影响发育和组织稳态，以及其改变如何导致许多不同人类疾病，特别是癌症的发生和发展。
