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Expression Specificity of Disease-Associated lncRNAs: Toward Personalized Medicine

  • Quan Nguyen
  • Piero CarninciEmail author
Part of the Current Topics in Microbiology and Immunology book series (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.

Keywords

Zinc Finger Nuclease lncRNA Expression lncRNA Locus Fantom Project Papillary Thyroid Carcinoma Susceptibility Candidate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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

Notes

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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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Division of Genomic Technologies, RIKEN Yokohama CampusRIKEN Center for Life Science TechnologiesYokohama CityJapan

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