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Bast-Habersbrunner, A.* ; Kiefer, C.* ; Weber, P. ; Fromme, T.* ; Schießl, A.* ; Schwalie, P.C.* ; Deplancke, B.* ; Li, Y.* ; Klingenspor, M.*

LncRNA Ctcflos orchestrates transcription and alternative splicing in thermogenic adipogenesis.

EMBO Rep.:e51289 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The recruitment of thermogenic brite adipocytes within white adipose tissue attenuates obesity and metabolic comorbidities, arousing interest in understanding the underlying regulatory mechanisms. The molecular network of brite adipogenesis, however, remains largely unresolved. In this light, long noncoding RNAs (lncRNAs) emerged as a versatile class of modulators that control many steps within the differentiation machinery. Leveraging the naturally varying propensities of different inbred mouse strains for white adipose tissue browning, we identify the nuclear lncRNA Ctcflos as a pivotal orchestrator of thermogenic gene expression during brite adipocyte differentiation. Mechanistically, Ctcflos acts as a pleiotropic regulator, being essential for the transcriptional recruitment of the early core thermogenic regulatory program and the modulation of alternative splicing to drive brite adipogenesis. This is showcased by Ctcflos-regulated gene transcription and splicing of the key browning factor Prdm16 toward the isoform that is specific for the thermogenic gene program. Conclusively, our findings emphasize the mechanistic versatility of lncRNAs acting at several independent levels of gene expression for effective regulation of key differentiation factors to direct cell fate and function.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Brite Adipocytes ; Long Noncoding Rnas ; Prdm16 ; Splicing ; Ucp1-dependent Thermogenesis; Brown Adipose-tissue; Long Noncoding Rna; De-novo Reconstruction; White Fat; Cold-exposure; Adipocytes; Prdm16; Mouse; Gene; Identification
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Quellenangaben Volume: , Issue: , Pages: , Article Number: e51289 Supplement: ,
Publisher EMBO Press
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Translational Metabolic Oncology (TMO)
Grants Else Kröner-Fresenius-Stiftung (EKFS)
German Obesity Competence Network
Deutsche Forschungsgemeinschaft (DFG)