Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Sci Transl Med. 2018 Jun 20;10(446). doi: 10.1126/scitranslmed.aar5987.
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 ( = 53) in patients after bariatric surgery were nonconserved. The most abundant adipose-enriched lincRNA in our subcutaneous adipose data set, , was nonconserved, up-regulated in adipose depots of obese individuals, and markedly induced during in vitro human adipocyte differentiation. We demonstrated that 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.
长链非编码 RNA（lncRNA）已成为细胞功能的重要调节因子。大多数 lncRNA 在哺乳动物中没有保守性，这就提出了一个基本问题，即非保守性脂肪组织表达的 lncRNA 是否具有功能。为了解决这个问题，我们对 25 名健康人的臀下皮下脂肪组织进行了深度 RNA 测序。通过从头构建非编码转录组并与现有 lincRNA 注释整合，我们在所有样本中鉴定出了 1001 个假定的 lincRNA。120 个 lincRNA 在脂肪组织中表达丰富，其中 54 个在其基因座上具有过氧化物酶体增殖物激活受体γ（PPARγ）或 CCAAT/增强子结合蛋白α（C/EBPα）结合。这些脂肪组织中表达丰富的 lincRNA 中有~85%在小鼠中没有保守，但平均而言，它们的 PPARγ 和 C/EBPα 表达和结合程度与保守 lincRNA 相似。大多数在肥胖患者接受减肥手术后差异表达的脂肪 lincRNA（=53）是非保守的。在我们的皮下脂肪数据集中，表达最丰富的脂肪组织特异性 lincRNA ，是非保守的，在肥胖个体的脂肪组织中上调，并在体外人脂肪细胞分化过程中明显诱导。我们证明了 与异质核核糖核蛋白 U（hnRNPU）和胰岛素样生长因子 2 mRNA 结合蛋白 2（IGF2BP2）在不同的亚细胞位置相互作用，以调节脂肪细胞分化和脂肪生成。
