Journal
CELL METABOLISM
Volume 21, Issue 5, Pages 764-776Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2015.04.003
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Funding
- Singapore NRF [NRF-2011NRF-NRFF 001-025]
- NIH [DK047618, DK068348, 5P01 HL066105]
- Singapore National Research Foundation under CBRG [NMRC/CBRG/0070/2014]
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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 similar to 1,500 lncRNAs, including 127 BAT-restricted loci induced during differentiation and often targeted by key regulators PPAR gamma, C/EBP alpha, and C/EBP beta. 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.
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