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 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)

1 RNMCD - Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011
2 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
3 FRABio - Biochimie Structurale et Fonctionnelle des Assemblages Biomoléculaires - CNRS FR3688
4 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
5 RTD - Recherche translationnelle sur le diabète - U 1190

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.

Domaines: Sciences du Vivant [q-bio]

François Firmin, Frédérik Oger, Celine Gheeraert, Julie Dubois 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, 2017, 7 (1), pp.14087. ⟨10.1038/s41598-017-14570-y⟩. ⟨inserm-02159068⟩