Ribosome biogenesis gene DEF/UTP25 is essential for liver homeostasis and regeneration
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bosome biogenesis gene DEF/UTP25 is essential for liver homeostasis and regeneration 1
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Weidong Huang , Feng Chen , Quanxin Ma , Jiaojiao Xin , Jiaqi Li , Jun Chen , Bin Zhou , 2* 3* 1* Minli Chen , Jun Li & Jinrong Peng 1
MOE Key Laboratory of Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; Academy of Chinese Medicine/Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China; 3 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of 2
Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; 4 College of Life Sciences, Zhejiang University, Hangzhou 310058, China; 5 The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China Received November 14, 2019; accepted January 17, 2020; published online April 14, 2020
Hepatocytes are responsible for diverse metabolic activities in a liver. Proper ribosome biogenesis is essential to sustain the function of hepatocytes. There are approximately 200 factors involved in ribosome biogenesis; however, few studies have focused on the role of these factors in maintaining liver homeostasis. The digestive organ expansion factor (def) gene encodes a nucleolar protein Def that participates in ribosome biogenesis. In addition, Def forms a complex with cysteine protease Calpain3 (Capn3) and recruits Capn3 to the nucleolus to cleave protein targets. However, the function of Def has not been characterized in the mammalian digestive organs. In this report, we show that conditional knockout of the mouse def gene in hepatocytes causes cell morphology abnormality and constant infiltration of inflammatory cells in the liver. As age increases, the def conditional knockout liver displays multiple tissue damage foci and biliary hyperplasia. Moreover, partial hepatectomy leads to sudden acute death to the def conditional knockout mice and this phenotype is rescued by intragastric injection of the anti-inflammation drug dexamethasone one day before hepatectomy. Our results demonstrate that Def is essential for maintaining the liver homeostasis and liver regeneration capacity in mammals. Def (digestive-organ expansion factor), ribosome biogenesis, ribosomopathy, liver regeneration, bile duct hyperplasia, mouse Citation:
Huang, W., Chen, F., Ma, Q., Xin, J., Li, J., Chen, J., Zhou, B., Chen, M., Li, J., and Peng, J. (2020). Ribosome biogenesis gene DEF/UTP25 is essential for liver homeostasis and regeneration. Sci China Life Sci 63, https://doi.org/10.1007/s11427-019-1635-2
INTRODUCTION Ribosome is the machinery for protein synthesis in a cell. Eukaryotic ribosome contains 40S small subunit (SSU) and 60S large subunit (LSU). The 40S SSU is composed of 18S rRNA and ~33 ribosoma
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