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Cited by 2,738Cancer-related molecular mechanisms researchGenomics and Phylogenetic StudiesRNA Research and Splicing

The landscape of long noncoding RNAs in the human transcriptome

Open access
Iyer, Matthew K, Niknafs, Yashar S, Malik, Rohit, Singhal, Udit, Sahu, Anirban, Hosono, Yasuyuki, Barrette, Terrence R, Prensner, John R +11 more·2015·Nature Genetics
DOI 10.1038/ng.3192PMC PMC4417758
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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.

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  • A majority of novel TSSs were supported by spliced transcripts from RNA-seq and expressed sequence tags.

    “A majority of the novel TSSs were supported by spliced transcripts (see methods) from RNA-seq25,26 and expressed sequence tag27”

    From Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes (2023) · cites this paper as [26]

    The Results section, “Characterization of long RNAs” (page unavailable), reports alternative splicing and chromatin-mark enrichment near TSSs, but does not say that a majority of novel TSSs were supported by spliced transcripts. A search for expressed sequence tags also found no passage establishing that evidence for the claim. (LLM, conf=0.73)

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Sorted by citations

Authors
Iyer, M. K., Niknafs, Y. S., Malik, R., Singhal, U., Sahu, A., Hosono, Y., Barrette, T. R., Prensner, J. R., Evans, J. R., Zhao, S., Poliakov, A., Cao, X., Dhanasekaran, S. M., Wu, Y.-M., Robinson, D. R., Beer, D. G., Feng, F. Y., Iyer, H. K., & Chinnaiyan, A. M.
Affiliations
  • University of Michigan (US)
  • Howard Hughes Medical Institute (US)
  • Colorado State University (US)
Corresponding author
Chinnaiyan, Arul M
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2015-01-19
Volume
47
Issue
3
Pages
199-208
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.3192
PMC
PMC4417758
OpenAlex
W2029919331
Cited by
2,738
References
11
Citations by year
2026: 50 · 2025: 102 · 2024: 180 · 2023: 208 · 2022: 287 · 2021: 397 · 2020: 369 · 2019: 316 · 2018: 310 · 2017: 227 · 2016: 204 · 2015: 87
FWCI
26.97
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • University of Michigan
  • National Cancer Institute (P50-CA-69568, R01CA132874, F30CA180376, U01CA111275, P50CA069568, R01CA154365, P50CA186786)
  • National Institute of General Medical Sciences (T32GM007863, T32GM007315)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
long non-coding RNA, human transcriptome, lncRNA expression, ultraconserved elements, disease-associated SNPs, lineage-specific gene expression, differential gene expression, transcriptome assembly, biomarkers
MeSH terms
Cell Line, Humans, Neoplasms, Gene Expression, Sequence Analysis, RNA, Cell Line, Tumor, Transcriptome, RNA, Long Noncoding

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