RNA-binding protein PSPC1 promotes the differentiation-dependent nuclear export of adipocyte RNAs

• Published in: The Journal of clinical investigation Vol. 127; no. 3; pp. 987 - 1004
• Main Authors: Wang, Jiexin, Rajbhandari, Prashant, Damianov, Andrey, Han, Areum, Sallam, Tamer, Waki, Hironori, Villanueva, Claudio J, Lee, Stephen D, Nielsen, Ronni, Mandrup, Susanne, Reue, Karen, Young, Stephen G, Whitelegge, Julian, Saez, Enrique, Black, Douglas L, Tontonoz, Peter
• Format: Journal Article
• Language: English
• Published: American Society for Clinical Investigation 01.03.2017
• Subjects: Analysis; Gene expression; Protein binding; RNA sequencing; Transcription (Genetics)
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI89484.

A highly orchestrated gene expression program establishes the properties that define mature adipocytes, but the contribution of posttranscriptional factors to the adipocyte phenotype is poorly understood. Here we have shown that the RNA-binding protein PSPC1, a component of the paraspeckle complex, 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 number of adipocyte RNAs, including the RNA 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 displayed reduced lipid storage and adipose tissue mass and were 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.