2018
DOI: 10.1016/j.cmet.2017.12.010
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The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding

Abstract: 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 n… Show more

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Cited by 83 publications
(69 citation statements)
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References 83 publications
(97 reference statements)
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“…Accumulating evidence suggests that altogether peripheral clocks play a critical role in regulating glucose and lipid homeostasis . Of note, mutations in the essential clock genes BMAL1 and CLOCK cause various metabolic disorders, while perturbations of metabolic pathways in mice, fed with a high‐fat diet, dampen the amplitude of circadian oscillations and lengthen their period .…”
Section: Body Metabolism Is Orchestrated By Circadian Clocks In Rodenmentioning
confidence: 99%
See 1 more Smart Citation
“…Accumulating evidence suggests that altogether peripheral clocks play a critical role in regulating glucose and lipid homeostasis . Of note, mutations in the essential clock genes BMAL1 and CLOCK cause various metabolic disorders, while perturbations of metabolic pathways in mice, fed with a high‐fat diet, dampen the amplitude of circadian oscillations and lengthen their period .…”
Section: Body Metabolism Is Orchestrated By Circadian Clocks In Rodenmentioning
confidence: 99%
“…54 Accumulating evidence suggests that altogether peripheral clocks play a critical role in regulating glucose and lipid homeostasis. 50,53,[55][56][57] Of note, mutations in the essential clock genes BMAL1 and CLOCK 46,58 cause various metabolic disorders, while perturbations of metabolic pathways in mice, fed with a high-fat diet, dampen the amplitude of circadian oscillations and lengthen their period. 59 Moreover, the expression of circadian output genes dramatically changes in these animals, partly due to the inhibition of CLOCK-BMAL1 recruitment to chromatin and the activation of PPARγ.…”
Section: Body Metabolism Is Orchestrated By Circadian Clocks In Rodmentioning
confidence: 99%
“…Indeed, muscle-specific loss of BMAL1 directly leads to metabolic inefficiency, impairs muscle triglyceride biosynthesis, and causes accumulation of bioactive lipids and amino acids in mice. 128 Advanced approaches for circadian metabolomic and lipidomic studies reveal that a large number of metabolites are oscillating around-the-clock in rodents and in human tissues, plasma and saliva. 122 Liver-specific Bmal1KO leads to reduced lipid accumulation in hepatic cells via increased mRNA methylation, in particular of PPARα.…”
Section: Of Mammalian Physiology and Metabolismmentioning
confidence: 99%
“…127 Additionally, the RNA-binding protein NONO situated in liver cell nuclei couples the rhythmic expression of metabolic genes with nutrient levels, with NONO-deficient mice exhibiting impaired glucose tolerance as well as lower hepatic glycogen and lipid content. 128 Advanced approaches for circadian metabolomic and lipidomic studies reveal that a large number of metabolites are oscillating around-the-clock in rodents and in human tissues, plasma and saliva. 40,53,[129][130][131][132][133][134][135] Integrative metabolomic profiling of 8 mouse tissues, conducted around the clock upon physiological conditions or high-fat diet, further exemplifies this tight temporal orchestration of whole-body metabolism by nutrient intake.…”
Section: Dibnermentioning
confidence: 99%
“…Cells were treated with or without rosiglitazone for 6 h and lysed in Pro-Prep Protein Extraction Solution (Intron Biotechnology, Seoul, Korea) supplemented with 0.5 U RNaseOut (Thermo Fisher Scientific). Endogenous RNA-HuR complexes were immunoprecipitated under native conditions as previously described by Benegiamo et al (28) with modifications. Briefly, total cell lysates were incubated with Protein G Sepharose 4 Fast Flow resin (GE Healthcare) and normal mouse IgG or anti-HuR antibodies at 4°C.…”
Section: Rna Immunoprecipitationmentioning
confidence: 99%