De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development
Author(s)Bai, Zhiqiang; Xu, Dan; Yuan, Bingbing; Lo, Kinyui Alice; Yoon, Myeong Jin; Lim, Yen Ching; Knoll, Marko; Chen, Shuai; Chen, Peng; Sun, Lei; Alvarez, Juan Rene; Slavov, Nikolai G; Lodish, Harvey F; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Alvarez-Dominguez, Juan R. et al. “De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-Coding RNA Regulators of Brown Adipocyte Development.” Cell Metabolism 21.5 (2015): 764–776.
Author's final manuscript