Journal
CELL METABOLISM
Volume 27, Issue 2, Pages 404-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2017.12.010
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Funding
- Glenn Center for Aging Research
- Swiss National Science Foundation (SNF) [P1ZHP3_168431]
- Paul F. Glenn Center for Biology of Aging Research at the Salk Institute
- Helmsley Foundation
- American Federation for Aging Research grant [M14322]
- Waitt Advanced Biophotonics Core
- GT3 Core
- Razavi Newman Integrative Genomics and Bioinformatics Core
- Mass Spectrometry Core
- NGS Core of the Salk Institute
- NIH-NCI CCSG [P30 014195]
- NINDS Neuroscience Core Grant [NS072031]
- Waitt Foundation
- NINDS Core Grant [R24NS092943]
- Chapman Foundation
- Helmsley Center for Genomic Medicine
- SNF
- Hartmann-Mueller Foundation
- NATIONAL CANCER INSTITUTE [P30CA014195] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R24NS092943] Funding Source: NIH RePORTER
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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.
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