Pulmonary Hypertension and Vascular Biology Research Group, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Department of Medicine, Université Laval, Quebec City, Quebec, Canada.
Department of Medicine, Université Laval, Quebec City, Quebec, Canada.
Am J Physiol Cell Physiol. 2020 Jan 1;318(1):C1-C28. doi: 10.1152/ajpcell.00078.2019. Epub 2019 Sep 4.
Although a majority of the mammalian genome is transcribed to RNA, mounting evidence indicates that only a minor proportion of these transcriptional products are actually translated into proteins. Since the discovery of the first non-coding RNA (ncRNA) in the 1980s, the field has gone on to recognize ncRNAs as important molecular regulators of RNA activity and protein function, knowledge of which has stimulated the expansion of a scientific field that quests to understand the role of ncRNAs in cellular physiology, tissue homeostasis, and human disease. Although our knowledge of these molecules has significantly improved over the years, we have limited understanding of their precise functions, protein interacting partners, and tissue-specific activities. Adding to this complexity, it remains unknown exactly how many ncRNAs there are in existence. The increased use of high-throughput transcriptomics techniques has rapidly expanded the list of ncRNAs, which now includes classical ncRNAs (e.g., ribosomal RNAs and transfer RNAs), microRNAs, and long ncRNAs. In addition, splicing by-products of protein-coding genes and ncRNAs, so-called circular RNAs, are now being investigated. Because there is substantial heterogeneity in the functions of ncRNAs, we have summarized the present state of knowledge regarding the functions of ncRNAs in heart, lungs, and skeletal muscle. This review highlights the pathophysiologic relevance of these ncRNAs in the context of human cardiovascular, pulmonary, and muscle diseases.
尽管大多数哺乳动物基因组都转录成 RNA,但越来越多的证据表明,这些转录产物只有一小部分实际上被翻译成蛋白质。自 20 世纪 80 年代发现第一个非编码 RNA(ncRNA)以来,该领域已将 ncRNA 识别为 RNA 活性和蛋白质功能的重要分子调节剂,这方面的知识促进了一个科学领域的扩展,该领域旨在了解 ncRNA 在细胞生理学、组织稳态和人类疾病中的作用。尽管我们多年来对这些分子的了解有了显著提高,但我们对它们的确切功能、蛋白相互作用伙伴和组织特异性活性仍知之甚少。更复杂的是,目前尚不清楚这些分子的存在数量。高通量转录组学技术的广泛应用迅速扩大了 ncRNA 的名单,其中包括经典 ncRNA(如核糖体 RNA 和转运 RNA)、microRNA 和长 ncRNA。此外,现在正在研究蛋白编码基因和 ncRNA 的剪接产物,即所谓的环状 RNA。由于 ncRNA 的功能具有很大的异质性,我们总结了 ncRNA 在心脏、肺和骨骼肌中的功能的现有知识状态。这篇综述强调了这些 ncRNA 在人类心血管、肺部和肌肉疾病中的病理生理学相关性。