DiStefano Johanna K
Translational Genomics Research Institute, 445 N 5th St, Phoenix, AZ, 85004, USA.
Methods Mol Biol. 2018;1706:91-110. doi: 10.1007/978-1-4939-7471-9_6.
Only a small fraction of the human genome corresponds to protein-coding genes. Historically, the vast majority of genomic sequence was dismissed as transcriptionally silent, but recent large-scale investigations have instead revealed a rich array of functionally significant elements, including non-protein-coding transcripts, within the noncoding regions of the human genome. Long noncoding RNAs (lncRNAs), a class of noncoding transcripts with lengths >200 nucleotides, are pervasively transcribed in the genome, and have been shown to bind DNA, RNA, and protein. LncRNAs exert effects through a variety of mechanisms that include guiding chromatin-modifying complexes to specific genomic loci, providing molecular scaffolds, modulating transcriptional programs, and regulating miRNA expression. An increasing number of experimental studies are providing evidence that lncRNAs mediate disease pathogenesis, thereby challenging the concept that protein-coding genes are the sole contributors to the development of human disease. This chapter highlights recent findings linking lncRNAs with human diseases of complex etiology, including hepatocellular carcinoma, Alzheimer's disease, and diabetes.
只有一小部分人类基因组对应于蛋白质编码基因。从历史上看，绝大多数基因组序列被认为是转录沉默的，但最近的大规模研究反而揭示了人类基因组非编码区域内丰富的一系列功能重要元件，包括非蛋白质编码转录本。长链非编码RNA（lncRNA）是一类长度大于200个核苷酸的非编码转录本，在基因组中广泛转录，并已被证明可与DNA、RNA和蛋白质结合。lncRNA通过多种机制发挥作用，包括将染色质修饰复合物引导至特定基因组位点、提供分子支架、调节转录程序以及调控miRNA表达。越来越多的实验研究提供了证据，表明lncRNA介导疾病发病机制，从而挑战了蛋白质编码基因是人类疾病发展唯一贡献者的概念。本章重点介绍了将lncRNA与复杂病因的人类疾病（包括肝细胞癌、阿尔茨海默病和糖尿病）联系起来的最新发现。
