De novo Reconstruction of Adipose Tissue Transcriptomes Reveals Novel Long Non-coding RNAs that Regulate Brown Adipocyte Development

• Published in: Cell metabolism Vol. 21; no. 5; pp. 764 - 776
• 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, Peng, Chen, Lodish, Harvey F., Sun, Lei
• Format: Journal Article
• Language: English
• Published: 23-04-2015
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2015.04.003

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 ~1500 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, available online, and establishes lnc-BATE1 as a novel regulator of BAT development and physiology.