Diabetes and Obesity Center.
The Christina Lee Brown Envirome Institute, Department of Medicine.
Curr Opin Cardiol. 2020 May;35(3):199-206. doi: 10.1097/HCO.0000000000000725.
Mounting evidence suggests that long noncoding RNAs (lncRNAs) are essential regulators of gene expression. Although few lncRNAs have been the subject of detailed molecular and functional characterization, it is believed that lncRNAs play an important role in tissue homeostasis and development. In fact, gene expression profiling studies reveal lncRNAs are developmentally regulated in a tissue-type and cell-type specific manner. Such findings have brought significant attention to their potential contribution to disease cause. The current review summarizes recent studies of lncRNAs in the heart.
lncRNA discovery has largely been driven by the implementation of next generation sequencing technologies. To date, such technologies have contributed to the identification of tens of thousands of distinct lncRNAs in humans -- accounting for a large majority of all RNA sequences transcribed across the human genome. Although the functions of these lncRNAs remain largely unknown, gain-of-function and loss-of-function studies (in vivo and in vitro) have uncovered a number of mechanisms by which lncRNAs regulate gene expression and protein function. Such mechanisms have been stratified according to three major functional categories: RNA sponges (RNA-mediated sequestration of free miRNAs; e.g. H19, MEG3, and MALAT1); transcription-modulating lncRNAs (RNA influences regulatory factor recruitment by binding to histone modifiers or transcription factors; e.g. CAIF, MANTIS, and NEAT1); and translation-modulating lncRNAs (RNA modifies protein function via directly interacting with a protein itself or binding partners; e.g. Airn, CCRR, and ZFAS1).
Recent studies strongly suggest that lncRNAs function via binding to macromolecules (e.g. genomic DNA, miRNAs, or proteins). Thus, lncRNAs constitute an additional mode by which cells regulate gene expression.
越来越多的证据表明长链非编码 RNA（lncRNA）是基因表达的重要调控因子。虽然只有少数 lncRNA 得到了详细的分子和功能特征描述，但人们相信 lncRNA 在组织稳态和发育中发挥着重要作用。事实上，基因表达谱研究表明，lncRNA 以组织和细胞类型特异性的方式进行发育调控。这些发现引起了人们对它们在疾病发病机制中潜在作用的极大关注。本综述总结了近年来心脏 lncRNA 的研究进展。
lncRNA 的发现主要得益于下一代测序技术的应用。迄今为止，这些技术已经在人类中鉴定了数万个独特的 lncRNA，占人类基因组转录的大多数 RNA 序列。尽管这些 lncRNA 的功能仍知之甚少，但功能获得和功能丧失研究（体内和体外）揭示了 lncRNA 调节基因表达和蛋白质功能的许多机制。这些机制根据三个主要功能类别进行了分层：RNA 海绵（RNA 介导游离 miRNA 的隔离；例如 H19、MEG3 和 MALAT1）；转录调节 lncRNA（RNA 通过与组蛋白修饰物或转录因子结合来影响调节因子的募集；例如 CAIF、MANTIS 和 NEAT1）；和翻译调节 lncRNA（RNA 通过直接与蛋白质本身或结合伴侣相互作用来改变蛋白质功能；例如 Airn、CCRR 和 ZFAS1）。
最近的研究强烈表明，lncRNA 通过与大分子（例如基因组 DNA、miRNA 或蛋白质）结合发挥作用。因此，lncRNA 构成了细胞调节基因表达的另一种方式。
