The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding

Benegiamo Giorgia; Mure Ludovic S.; Erikson Galina; Le Hiep D.; Moriggi Ermanno; Brown Steven A.; Panda Satchidananda

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The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding

机译：RNA结合蛋白壬二族坐标肝适应喂养

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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.

机译：进料和禁食的机制，用于在营养可用性中生理适应生理适应日常节律的节律基因的表达尚不清楚。在这里，我们表明，在喂食时，RNA结合蛋白的乳蛋白在肝细胞核中的斑点结构内积聚在斑点状结构内。结合RNA免疫沉淀和测序（RIP-SEQ），我们发现在喂养后的壬二次的增加数量的RNA。我们进一步表明，壬二结合和调节转录后营养代谢参与的基因的节奏性。最后，我们表明，非靶基因的有力节奏受到了深刻的代谢影响。实际上，缺乏缺乏小鼠表现出葡萄糖耐受性和低肝糖原和脂质的受损。因此，这些小鼠从葡萄糖储存转变为脂肪氧化，因此在整个成年期间保持倾向。总之，我们的研究表明，随后与饲养/禁食循环相比，诺托与喂养/禁食循环相邻的代谢基因的表达，从而在能量稳定性中发挥着关键作用。

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《Cell metabolism》 |2018年第2期|共22页
作者
Benegiamo Giorgia; Mure Ludovic S.; Erikson Galina; Le Hiep D.; Moriggi Ermanno; Brown Steven A.; Panda Satchidananda;
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Univ Zurich Inst Pharmacol &

Toxicol Chronobiol &

Sleep Res Grp Winterthurerstr 190 CH-8057;

Salk Inst Biol Studies Regulatory Biol Lab 10010 N Torrey Pines Rd La Jolla CA 92037 USA;

Salk Inst Biol Studies Razavi Newman Integrat Genom &

Bioinformat Core F 10010 N Torrey Pines Rd;

Salk Inst Biol Studies Regulatory Biol Lab 10010 N Torrey Pines Rd La Jolla CA 92037 USA;

Univ Zurich Inst Pharmacol &

Toxicol Chronobiol &

Sleep Res Grp Winterthurerstr 190 CH-8057;

Univ Zurich Inst Pharmacol &

Toxicol Chronobiol &

Sleep Res Grp Winterthurerstr 190 CH-8057;

Salk Inst Biol Studies Regulatory Biol Lab 10010 N Torrey Pines Rd La Jolla CA 92037 USA;

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正文语种 eng
中图分类内分泌腺疾病及代谢病;
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专利

1. The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding [J] . Benegiamo Giorgia, Mure Ludovic S., Erikson Galina, Cell metabolism . 2018,第2期

机译：RNA结合蛋白壬二族坐标肝适应喂养
2. Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes [J] . Li Shuyi, Shu Feng-jue, Li Zhentian, DNA repair . 2017,第期

机译：RNA结合蛋白的细胞型特异性作用，在小鼠睾丸中的DNA双链断裂响应中的RNA结合蛋白
3. PARP activation regulates the RNA-binding protein NONO in the DNA damage response to DNA double-strand breaks [J] . Krietsch Jana, Caron Marie-Christine, Gagne Jean-Philippe, Nucleic Acids Research . 2012,第20期

机译：PARP激活可调节DNA损伤对DNA双链断裂的反应中的RNA结合蛋白NONO
4. Function driven protein evolution. A possible proto-protein for the RNA-binding proteins [C] . Jacquelyn S. Fetrow, Adam Godzik Pacific Symposium on Biocomputing '98 4-9 January 1998 Maui, Hawaii, USA . 1998

机译：功能驱动的蛋白质进化。 RNA结合蛋白的可能原蛋白
5. Characterization of two RNA-binding proteins containing RNA-Recognition Motif (RRM)-type RNA-binding domains from mouse brain. [D] . Inman, Michael Verne. 1999

机译：表征两个RNA结合蛋白的小鼠大脑中的RNA识别基序（RRM）型RNA结合域。
6. RNA-binding protein NONO contributes to cancer cell growth and confers drug resistance as a theranostic target in TNBC [O] . Seong-Jin Kim, Jin-Sung Ju, Myoung-Hee Kang, 2020

机译：RNA结合蛋白NONO有助于癌细胞生长并赋予TNBC作为治疗目标的耐药性
7. Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes [O] . Shuyi Li, Feng-jue Shu, Zhentian Li, 2017

机译：RNA结合蛋白（NONO）在小鼠睾丸中的DNA双链断裂响应中的细胞型特异性作用
8. RNA-Binding Proteins as Novel Oncoproteins and Tumor Suppressors in Breast Cancer [R] . Brewer, G. 2006

机译：RNa结合蛋白作为乳腺癌中的新型癌蛋白和肿瘤抑制因子

The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding

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