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

Sci Rep. 2017 Oct 26;7(1):14087. doi: 10.1038/s41598-017-14570-y.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / metabolism*
  • Adipogenesis / physiology*
  • Adult
  • Animals
  • Body Mass Index
  • Cell Nucleus / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Inflammation
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Middle Aged
  • Obesity / metabolism
  • PPAR gamma / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Transcription Factors / metabolism*
  • Transcription, Genetic

Substances

  • Rbm14 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • PPAR gamma
  • RBM14 protein, human
  • RNA, Long Noncoding
  • Transcription Factors