Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
Byrd Alzheimer's Center & Research Institute, USF Health Neuroscience Institute, Tampa, FL, USA.
Neuromolecular Med. 2024 Mar 28;26(1):7. doi: 10.1007/s12017-024-08776-3.
Noncoding DNA undergoes widespread context-dependent transcription to produce noncoding RNAs. In recent decades, tremendous advances in genomics and transcriptomics have revealed important regulatory roles for noncoding DNA elements and the RNAs that they produce. Enhancers are one such element that are well-established drivers of gene expression changes in response to a variety of factors such as external stimuli, cellular responses, developmental cues, and disease states. They are known to act at long distances, interact with multiple target gene loci simultaneously, synergize with other enhancers, and associate with dynamic chromatin architectures to form a complex regulatory network. Recent advances in enhancer biology have revealed that upon activation, enhancers transcribe long noncoding RNAs, known as enhancer RNAs (eRNAs), that have been shown to play important roles in enhancer-mediated gene regulation and chromatin-modifying activities. In the brain, enhancer dysregulation and eRNA transcription has been reported in numerous disorders from acute injuries to chronic neurodegeneration. Because this is an emerging area, a comprehensive understanding of eRNA function has not yet been achieved in brain disorders; however, the findings to date have illuminated a role for eRNAs in activity-driven gene expression and phenotypic outcomes. In this review, we highlight the breadth of the current literature on eRNA biology in brain health and disease and discuss the challenges as well as focus areas and strategies for future in-depth research on eRNAs in brain health and disease.
非编码 DNA 经历广泛的上下文依赖转录,产生非编码 RNA。在最近几十年中,基因组学和转录组学的巨大进展揭示了非编码 DNA 元件及其产生的 RNA 的重要调控作用。增强子就是这样一个元件,它是响应各种因素(如外部刺激、细胞反应、发育线索和疾病状态)导致基因表达变化的公认驱动因素。已知它们可以远距离作用,同时与多个靶基因座相互作用,与其他增强子协同作用,并与动态染色质结构相互作用,形成复杂的调控网络。增强子生物学的最新进展表明,增强子在被激活后会转录长非编码 RNA,即增强子 RNA(eRNA),这些 RNA 已被证明在增强子介导的基因调控和染色质修饰活性中发挥重要作用。在大脑中,已经在许多从急性损伤到慢性神经退行性变的疾病中报道了增强子失调和 eRNA 转录。由于这是一个新兴领域,因此在大脑疾病中尚未全面了解 eRNA 的功能;然而,迄今为止的研究结果表明,eRNA 在活性驱动的基因表达和表型结果中发挥作用。在这篇综述中,我们强调了 eRNA 生物学在大脑健康和疾病中的当前文献的广度,并讨论了在大脑健康和疾病中对 eRNA 进行深入研究的挑战、重点领域和策略。