The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding

Publication date: Available online 18 January 2018
Source:Cell Metabolism
Author(s): Giorgia Benegiamo, Ludovic S. Mure, Galina Erikson, Hiep D. Le, Ermanno Moriggi, Steven A. Brown, Satchidananda Panda
The mechanisms by which feeding and fasting drive rhythmic gene expression for physiological adaptation to daily rhythm in nutrient availability are not well understood. Here we show that, upon feeding, the RNA-binding protein NONO accumulates within speckle-like structures in liver cell nuclei. Combining RNA-immunoprecipitation and sequencing (RIP-seq), we find that an increased number of RNAs are bound by NONO after feeding. We further show that NONO binds and regulates the rhythmicity of genes involved in nutrient metabolism post-transcriptionally. Finally, we show that disrupted rhythmicity of NONO target genes has profound metabolic impact. Indeed, NONO-deficient mice exhibit impaired glucose tolerance and lower hepatic glycogen and lipids. Accordingly, these mice shift from glucose storage to fat oxidation, and therefore remain lean throughout adulthood. In conclusion, our study demonstrates that NONO post-transcriptionally coordinates circadian mRNA expression of metabolic genes with the feeding/fasting cycle, thereby playing a critical role in energy homeostasis.

Graphical abstract

Teaser

Benegiamo et al. identify a metabolic role for the nuclear RNA-binding protein NONO. Upon feeding, NONO binds to pre-mRNAs of genes involved in glucose and fat metabolism in the liver, regulating their rhythmic expression post-transcriptionally. NONO-deficient mice exhibit disruptions in this temporal regulation and shift from glucose storage to fat oxidation.


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