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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)
Verlagsversion 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift EMBO Reports
Quellenangaben Band: , Heft: , Seiten: , Artikelnummer: e51289 Supplement: ,
Verlag EMBO Press
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Translational Metabolic Oncology (TMO)
Förderungen Else Kröner-Fresenius-Stiftung (EKFS)
German Obesity Competence Network
Deutsche Forschungsgemeinschaft (DFG)