The RBM14/CoAA-interacting, long intergenic non-coding RNA Paral1 regulates adipogenesis and coactivates the nuclear receptor PPARγ

François Firmin 1 Frédérik Oger 1 Celine Gheeraert 1 Julie Dubois-Chevalier 1 Anne-Sophie Vercoutter-Edouart 2, 3 Fawaz Alzaid 4 Claire Mazuy 1 Hélène Dehondt 1 Jérémy Alexandre 1 Bruno Derudas 1 Quentin Dhalluin 1 Maheul Ploton 1 Alexandre Berthier 1 Eloise Woitrain 1 Tony Lefebvre 2 Nicolas Venteclef 4 François Pattou 5 Bart Staels 1 Jérôme Eeckhoute 1 Philippe Lefebvre 1, *
* Corresponding author
1 EGID - Récepteurs nucléaires, maladies cardiovasculaires et diabète
2 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
3 FRABio - CNRS FR3688 - Fédération de Recherche Biochimie Structurale et Fonctionnelle des Assemblages Biomoléculaires
4 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
5 EGID - Recherche translationelle sur le diabète
Abstract : Adipocyte differentiation and function relies on a network of transcription factors, which is disrupted in obesity-associated low grade, chronic inflammation leading to adipose tissue dysfunction. In this context, there is a need for a thorough understanding of the transcriptional regulatory network involved in adipose tissue pathophysiology. Recent advances in the functional annotation of the genome has highlighted the role of non-coding RNAs in cellular differentiation processes in coordination with transcription factors. Using an unbiased genome-wide approach, we identified and characterized a novel long intergenic non-coding RNA (lincRNA) strongly induced during adipocyte differentiation. This lincRNA favors adipocyte differentiation and coactivates the master adipogenic regulator peroxisome proliferator-activated receptor gamma (PPARγ) through interaction with the paraspeckle component and hnRNP-like RNA binding protein 14 (RBM14/NCoAA), and was therefore called PPARγ-activator RBM14-associated lncRNA (Paral1). Paral1 expression is restricted to adipocytes and decreased in humans with increasing body mass index. A decreased expression was also observed in diet-induced or genetic mouse models of obesity and this down-regulation was mimicked in vitro by TNF treatment. In conclusion, we have identified a novel component of the adipogenic transcriptional regulatory network defining the lincRNA Paral1 as an obesity-sensitive regulator of adipocyte differentiation and function.
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François Firmin, Frédérik Oger, Celine Gheeraert, Julie Dubois-Chevalier, Anne-Sophie Vercoutter-Edouart, et al.. The RBM14/CoAA-interacting, long intergenic non-coding RNA Paral1 regulates adipogenesis and coactivates the nuclear receptor PPARγ. Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.14087. ⟨10.1038/s41598-017-14570-y⟩. ⟨inserm-02159068⟩

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