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Expression Specificity of Disease-Associated lncRNAs: Toward Personalized Medicine

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Long Non-coding RNAs in Human Disease

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 394))

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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Abbreviations

CAGE:

Cap analysis of gene expression

ChIP:

Chromatin immunoprecipitation

ENCODE:

Encyclopedia of DNA elements

eRNAs:

Enhancer RNAs

FANTOM:

Functional annotation of mammalian genome

GWAS:

Genome-wide association study

lncRNAs:

Long noncoding RNAs

miRNAs:

MicroRNAs

TSS:

Transcription start sites

RNA-seq:

RNA sequencing

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Acknowledgements

We especially thank FANTOM consortium for generating unprecedented amount of data for promoter-centric analysis in thousands of samples. We apologize for not being able to mention all important, related work from colleagues. This work was supported by a research grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) to the RIKEN Center for Life Science Technologies and the Human Frontier Science Program to P.C.

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  1. 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

    Quan Nguyen & Piero Carninci

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  1. Quan Nguyen
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  2. Piero Carninci
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Correspondence to Piero Carninci .

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  1. City of Hope - Beckman Research Institute, Center for Gene Therapy City of Hope-Beckman Research Institute, Duarte, California, USA

    Kevin V. Morris

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Nguyen, Q., Carninci, P. (2015). Expression Specificity of Disease-Associated lncRNAs: Toward Personalized Medicine. In: Morris, K. (eds) Long Non-coding RNAs in Human Disease. Current Topics in Microbiology and Immunology, vol 394. Springer, Cham. https://doi.org/10.1007/82_2015_464

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