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Spliceosome component Usp39 contributes to hepatic lipid homeostasis through the regulation of autophagy.
Cui, Donghai; Wang, Zixiang; Dang, Qianli; Wang, Jing; Qin, Junchao; Song, Jianping; Zhai, Xiangyu; Zhou, Yachao; Zhao, Ling; Lu, Gang; Liu, Hongbin; Liu, Gang; Liu, Runping; Shao, Changshun; Zhang, Xiyu; Liu, Zhaojian.
Afiliación
  • Cui D; Key Laboratory of Experimental Teratology, Ministry of Education, School of Basic Medical Science, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
  • Wang Z; Advanced Medical Research Institute, Shandong University, Jinan, China.
  • Dang Q; Key Laboratory of Experimental Teratology, Ministry of Education, School of Basic Medical Science, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
  • Wang J; Advanced Medical Research Institute, Shandong University, Jinan, China.
  • Qin J; Key Laboratory of Experimental Teratology, Ministry of Education, School of Basic Medical Science, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
  • Song J; Advanced Medical Research Institute, Shandong University, Jinan, China.
  • Zhai X; Key Laboratory of Experimental Teratology, Ministry of Education, School of Basic Medical Science, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
  • Zhou Y; Advanced Medical Research Institute, Shandong University, Jinan, China.
  • Zhao L; Key Laboratory of Experimental Teratology, Ministry of Education, School of Basic Medical Science, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
  • Lu G; Advanced Medical Research Institute, Shandong University, Jinan, China.
  • Liu H; Department of General Surgery, The Second Hospital, Shandong University, Jinan, China.
  • Liu G; Department of General Surgery, The Second Hospital, Shandong University, Jinan, China.
  • Liu R; Key Laboratory of Experimental Teratology, Ministry of Education, School of Basic Medical Science, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
  • Shao C; Advanced Medical Research Institute, Shandong University, Jinan, China.
  • Zhang X; Key Laboratory of Experimental Teratology, Ministry of Education, School of Basic Medical Science, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
  • Liu Z; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Nat Commun ; 14(1): 7032, 2023 11 03.
Article en En | MEDLINE | ID: mdl-37923718
Regulation of alternative splicing (AS) enables a single transcript to yield multiple isoforms that increase transcriptome and proteome diversity. Here, we report that spliceosome component Usp39 plays a role in the regulation of hepatocyte lipid homeostasis. We demonstrate that Usp39 expression is downregulated in hepatic tissues of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) subjects. Hepatocyte-specific Usp39 deletion in mice leads to increased lipid accumulation, spontaneous steatosis and impaired autophagy. Combined analysis of RNA immunoprecipitation (RIP-seq) and bulk RNA sequencing (RNA-seq) data reveals that Usp39 regulates AS of several autophagy-related genes. In particular, deletion of Usp39 results in alternative 5' splice site selection of exon 6 in Heat shock transcription factor 1 (Hsf1) and consequently its reduced expression. Importantly, overexpression of Hsf1 could attenuate lipid accumulation caused by Usp39 deficiency. Taken together, our findings indicate that Usp39-mediated AS is required for sustaining autophagy and lipid homeostasis in the liver.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Empalmosomas / Enfermedad del Hígado Graso no Alcohólico Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Empalmosomas / Enfermedad del Hígado Graso no Alcohólico Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido