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Sci Transl Med. 2018 Jun 20;10(446). pii: eaar5987. doi: 10.1126/scitranslmed.aar5987.

Interrogation of nonconserved human adipose lincRNAs identifies a regulatory role of linc-ADAL in adipocyte metabolism.

Author information

1
Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
2
Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
3
Division of Cardiovascular Medicine, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
4
Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
6
Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
7
Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing 100029, China.
8
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
9
The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
10
Divisions of Human Genetics and Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45267, USA.
11
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
12
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
13
Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA. mpr2144@cumc.columbia.edu.
14
Irving Institute for Clinical and Translational Research, Columbia University, New York, NY 10032, USA.

Abstract

Long intergenic noncoding RNAs (lincRNAs) have emerged as important modulators of cellular functions. Most lincRNAs are not conserved among mammals, raising the fundamental question of whether nonconserved adipose-expressed lincRNAs are functional. To address this, we performed deep RNA sequencing of gluteal subcutaneous adipose tissue from 25 healthy humans. We identified 1001 putative lincRNAs expressed in all samples through de novo reconstruction of noncoding transcriptomes and integration with existing lincRNA annotations. One hundred twenty lincRNAs had adipose-enriched expression, and 54 of these exhibited peroxisome proliferator-activated receptor γ (PPARγ) or CCAAT/enhancer binding protein α (C/EBPα) binding at their loci. Most of these adipose-enriched lincRNAs (~85%) were not conserved in mice, yet on average, they showed degrees of expression and binding of PPARγ and C/EBPα similar to those displayed by conserved lincRNAs. Most adipose lincRNAs differentially expressed (n = 53) in patients after bariatric surgery were nonconserved. The most abundant adipose-enriched lincRNA in our subcutaneous adipose data set, linc-ADAL, was nonconserved, up-regulated in adipose depots of obese individuals, and markedly induced during in vitro human adipocyte differentiation. We demonstrated that linc-ADAL interacts with heterogeneous nuclear ribonucleoprotein U (hnRNPU) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) at distinct subcellular locations to regulate adipocyte differentiation and lipogenesis.

PMID:
29925637
PMCID:
PMC6620026
DOI:
10.1126/scitranslmed.aar5987
[Indexed for MEDLINE]
Free PMC Article

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