De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development

• Main Authors: Alvarez-Dominguez, Juan R., Bai, Zhiqiang, Xu, Dan, Yuan, Bingbing, Lo, Kinyui Alice, Yoon, Myeong Jin, Lim, Yen Ching, Knoll, Marko, Slavov, Nikolai, Chen, Shuai, Chen, Peng, Lodish, Harvey F., Sun, Lei
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2016
• Subjects: Cell Metabolism
• Online Access: https://hdl.handle.net/10356/81866; http://hdl.handle.net/10220/39722
• Institution: Nanyang Technological University

Brown adipose tissue (BAT) protects against obesity by promoting energy expenditure via uncoupled respiration. To uncover BAT-specific long non-coding RNAs (lncRNAs), we used RNA-seq to reconstruct de novo transcriptomes of mouse brown, inguinal white, and epididymal white fat and identified ∼1,500 lncRNAs, including 127 BAT-restricted loci induced during differentiation and often targeted by key regulators PPARγ, C/EBPα, and C/EBPβ. One of them, lnc-BATE1, is required for establishment and maintenance of BAT identity and thermogenic capacity. lnc-BATE1 inhibition impairs concurrent activation of brown fat and repression of white fat genes and is partially rescued by exogenous lnc-BATE1 with mutated siRNA-targeting sites, demonstrating a function in trans. We show that lnc-BATE1 binds heterogeneous nuclear ribonucleoprotein U and that both are required for brown adipogenesis. Our work provides an annotated catalog for the study of fat depot-selective lncRNAs and establishes lnc-BATE1 as a regulator of BAT development and physiology.