The landscape of long noncoding RNAs in the human transcriptome

Matthew K Iyer; Yashar S Niknafs; Rohit Malik; Udit Singhal; Anirban Sahu; Yasuyuki Hosono; Terrence R Barrette; John R Prensner; Joseph R Evans; Shuang Zhao; Anton Poliakov; Xuhong Cao; Saravana M Dhanasekaran; Yi-Mi Wu; Dan R Robinson; David G Beer; Felix Y Feng; Hariharan K Iyer; Arul M Chinnaiyan

doi:10.1038/ng.3192

The landscape of long noncoding RNAs in the human transcriptome

Nat Genet. 2015 Mar;47(3):199-208. doi: 10.1038/ng.3192. Epub 2015 Jan 19.

Authors

Matthew K Iyer¹, Yashar S Niknafs², Rohit Malik³, Udit Singhal⁴, Anirban Sahu³, Yasuyuki Hosono⁵, Terrence R Barrette⁵, John R Prensner⁵, Joseph R Evans⁶, Shuang Zhao⁶, Anton Poliakov⁵, Xuhong Cao⁴, Saravana M Dhanasekaran³, Yi-Mi Wu⁵, Dan R Robinson⁵, David G Beer⁷, Felix Y Feng⁸, Hariharan K Iyer⁹, Arul M Chinnaiyan¹⁰

Affiliations

¹ 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Computational Medicine and Bioinformatics, Ann Arbor, Michigan, USA.
² 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA.
³ 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
⁴ 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
⁶ 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
⁷ 1] Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA. [2] Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
⁸ 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA. [3] Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.
⁹ Department of Statistics, Colorado State University, Fort Collins, Colorado, USA.
¹⁰ 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Computational Medicine and Bioinformatics, Ann Arbor, Michigan, USA. [3] Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA. [4] Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA. [5] Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA. [6] Department of Urology, University of Michigan, Ann Arbor, Michigan, USA.

PMID: 25599403
PMCID: PMC4417758
DOI: 10.1038/ng.3192

Abstract

Long noncoding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes including cancer. To delineate genome-wide lncRNA expression, we curated 7,256 RNA sequencing (RNA-seq) libraries from tumors, normal tissues and cell lines comprising over 43 Tb of sequence from 25 independent studies. We applied ab initio assembly methodology to this data set, yielding a consensus human transcriptome of 91,013 expressed genes. Over 68% (58,648) of genes were classified as lncRNAs, of which 79% were previously unannotated. About 1% (597) of the lncRNAs harbored ultraconserved elements, and 7% (3,900) overlapped disease-associated SNPs. To prioritize lineage-specific, disease-associated lncRNA expression, we employed non-parametric differential expression testing and nominated 7,942 lineage- or cancer-associated lncRNA genes. The lncRNA landscape characterized here may shed light on normal biology and cancer pathogenesis and may be valuable for future biomarker development.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cell Line
Cell Line, Tumor
Gene Expression
Humans
Neoplasms / genetics
RNA, Long Noncoding / genetics*
Sequence Analysis, RNA / methods
Transcriptome*

Substances

RNA, Long Noncoding

Abstract

Publication types

MeSH terms

Substances

Grants and funding