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The paraspeckle protein Pspc1 promotes adipogenesis through differentiation-dependent nuclear export of adipogenic RNAs

  • Author(s): Wang, Jiexin
  • Advisor(s): Tontonoz, Peter John
  • et al.
Abstract

Adipocyte differentiation is accompanied by a robust program of cell-type specific gene expression. Although transcriptional regulators of this process are well defined, the contribution of posttranscriptional factors to the establishment of the adipocyte phenotype is poorly understood. This thesis presents the RNA-binding protein paraspeckle protein 1 (Pspc1), a component of the paraspeckle complex, that promotes adipogenesis in vitro and is important for mature adipocyte function in vivo. Cross-linking and immunoprecipitation followed by RNA sequencing revealed that Pspc1 binds to intronic and 3′ untranslated regions of a battery of adipocyte RNAs, including that encoding the transcriptional regulator Ebf1. Purification of the paraspeckle complex from adipocytes further showed that Pspc1 associates with the RNA export factor Ddx3x in a differentiation-dependent manner. Remarkably, Pspc1 relocates from the nucleus to the cytoplasm during differentiation, coinciding with enhanced export of adipogenic RNAs. Mice lacking Pspc1 in fat show reduced lipid storage and adipose tissue mass and are resistant to diet-induced obesity and insulin resistance due to a compensatory increase in energy expenditure. These findings highlight a role for Pspc1-dependent RNA maturation in the posttranscriptional control of adipose development and function.

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