Nguyen Quan, Carninci Piero
Division of Genomic Technologies, RIKEN Yokohama Campus, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-Cho, Tsurumi-Ku, Yokohama City, Kanagawa, 230-0045, Japan.
Curr Top Microbiol Immunol. 2016;394:237-58. doi: 10.1007/82_2015_464.
Long noncoding RNAs (lncRNAs) perform diverse regulatory functions in transcription, translation' chromatin modification, and cellular organization. Misregulation of lncRNAs is found linked to various human diseases. Compared to protein-coding RNAs' lncRNAs are more specific to organs, tissues, cell types, developmental stages, and disease conditions' making them promising candidates as diagnostic and prognostic biomarkers and as gene therapy targets. The functional annotation of mammalian genome (FANTOM) consortium utilizes cap analysis of gene expression (CAGE) method to quantify genome-wide activities of promoters and enhancers of coding and noncoding RNAs across a large collection of human and mouse tissues' cell types' diseases, and time-courses. The project discovered widespread transcription of major lncRNA classes, including lncRNAs derived from enhancers' bidirectional promoters' antisense lncRNAs' and repetitive elements. Results from FANTOM project enable assessment of lncRNA expression specificity across tissue and disease conditions' based on differential promoter and enhancer usage. More than 85 % of disease-related SNPs are within noncoding regions and are strikingly overrepresented in enhancer and promoter regions, suggestive of the importance of lncRNA loci at these SNP harboring regions to human diseases. In this chapter' we discuss lncRNA expression specificity' review diverse functions of disease-associated lncRNAs' and present perspectives on their potential therapeutic applications for personalized medicine. The future development of lncRNA applications relies on technologies to identify and validate their functions' structures' and mechanisms. Comprehensive understanding of genome-wide interaction networks of lncRNAs with proteins, chromatins, and other RNAs in regulating cellular processes will allow personalized medicine to use lncRNAs as highly specific biomarkers in diagnosis' prognosis, and therapeutic targets.
长链非编码RNA（lncRNAs）在转录、翻译、染色质修饰和细胞组织中发挥着多种调控功能。lncRNAs的失调与多种人类疾病相关。与蛋白质编码RNA相比，lncRNAs对器官、组织、细胞类型、发育阶段和疾病状况更具特异性，这使其有望成为诊断和预后生物标志物以及基因治疗靶点。哺乳动物基因组功能注释（FANTOM）联盟利用基因表达帽分析（CAGE）方法，对大量人类和小鼠组织、细胞类型、疾病及时间进程中编码和非编码RNA的启动子和增强子的全基因组活性进行量化。该项目发现了主要lncRNA类别的广泛转录，包括源自增强子、双向启动子、反义lncRNAs和重复元件的lncRNAs。FANTOM项目的结果能够基于启动子和增强子的差异使用情况，评估lncRNA在不同组织和疾病状况下的表达特异性。超过85%的疾病相关单核苷酸多态性（SNPs）位于非编码区域，并且在增强子和启动子区域显著富集，这表明这些携带SNP的区域中的lncRNA基因座对人类疾病具有重要意义。在本章中，我们讨论lncRNA的表达特异性，综述疾病相关lncRNAs的多种功能，并阐述它们在个性化医学中潜在治疗应用的前景。lncRNA应用的未来发展依赖于识别和验证其功能、结构及机制的技术。全面了解lncRNAs与蛋白质、染色质和其他RNA在调节细胞过程中的全基因组相互作用网络，将使个性化医学能够将lncRNAs用作诊断、预后和治疗靶点的高度特异性生物标志物。
