HuR promotes triglyceride synthesis and intestinal fat absorption
Cihang Liu,
Yunping Lin,
Ying Wang,
Shuyong Lin,
Jing Zhou,
Hao Tang,
Xia Yi,
Zhengliang Ma,
Tianjiao Xia,
Bin Jiang,
Feng Tian,
Zhenyu Ju,
Baohua Liu,
Xiaoping Gu,
Zhongzhou Yang,
Wengong Wang
Affiliations
Cihang Liu
Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China
Yunping Lin
Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China
Ying Wang
Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China
Shuyong Lin
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China
Jing Zhou
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China
Hao Tang
National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Heart Center of Henan Provincial People’s Hospital, Central China Fuwai Hospital of Zhengzhou University, Central China Fuwai Hospital and Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou, Henan 450003, China
Xia Yi
Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China
Zhengliang Ma
Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China
Tianjiao Xia
Medical School, Nanjing University, Nanjing 210093, China
Bin Jiang
Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China
Feng Tian
Department of Laboratory Animal Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China
Zhenyu Ju
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China
Baohua Liu
Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Carson International Cancer Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen 518060, China
Xiaoping Gu
Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Corresponding author
Zhongzhou Yang
Medical School, Nanjing University, Nanjing 210093, China; Corresponding author
Wengong Wang
Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China; Center for Healthy Aging, Changzhi Medical College, Changzhi 046000, China; Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranostics, Collaborative Innovation Center for Age-related Disease, Life Science Institute of Jinzhou Medical University, Jinzhou 121001, Liaoning, China; Corresponding author
Summary: Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3′ UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3′ UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.
