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

Xuan Zhang, Chenyi Xue, Jennie Lin, Jane F. Ferguson, Amber Weiner, Wen Liu, Yumiao Han, Christine Hinkle, Wenjun Li, Hongfeng Jiang, Sager Gosai, Melanie Hachet, Benjamin A. Garcia, Brian D. Gregory, Raymond E. Soccio, John B. Hogenesch, Patrick Seale, Mingyao Li, Muredach P. Reilly*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 adiposeexpressed 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 ? (PPAR?) or CCAAT/enhancer binding protein ? (C/EBP?) 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 PPAR? and C/EBP? 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.

Original languageEnglish (US)
Article numberaar5987
JournalScience Translational Medicine
Volume10
Issue number44
DOIs
StatePublished - Jun 20 2018

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Interrogation of nonconserved human adipose lincRNAs identifies a regulatory role of linc-ADAL in adipocyte metabolism'. Together they form a unique fingerprint.

Cite this