The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding

Cell Metab. 2018 Feb 6;27(2):404-418.e7. doi: 10.1016/j.cmet.2017.12.010. Epub 2018 Jan 18.


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.

Keywords: DBHS protein; NOPS protein; circadian clock; diabetes; metabolic disorder; paraspeckle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological*
  • Adiposity / drug effects
  • Animals
  • Body Weight / drug effects
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / metabolism*
  • Feeding Behavior*
  • Gene Expression Regulation / drug effects
  • Glucose / pharmacology
  • Hepatocytes / metabolism
  • Homeostasis / drug effects
  • Introns / genetics
  • Liver / metabolism*
  • Mice, Inbred C57BL
  • Models, Biological
  • Protein Binding
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*


  • DNA-Binding Proteins
  • Nono protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • Glucose