Abstract
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.
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