| Autor: |
Donghai Cui, Zixiang Wang, Qianli Dang, Jing Wang, Junchao Qin, Jianping Song, Xiangyu Zhai, Ling Zhao, Gang Lu, Hongbin Liu, Runping Liu, Changshun Shao, Xiyu Zhang, Zhaojian Liu |
| Rok vydání: |
2023 |
| DOI: |
10.21203/rs.3.rs-2182223/v1 |
| Popis: |
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 critical role in the regulation of hepatocyte lipid homeostasis. We demonstrate that Usp39 expression is downregulated in hepatic tissues of NAFLD and non-alcoholic steatohepatitis (NASH) subjects. Hepatocyte-specific Usp39 deletion leads to increased lipid accumulation, spontaneous steatosis and impaired autophagy. Combined analysis of RIP-seq and RNA-seq data reveals that Usp39 regulates AS of several autophagy-related genes. For example, deletion of Usp39 results in alternative 5’ splice site selection of exon 6 in Heat shock transcription factor 1 (Hsf1) and consequently reduced expression. Importantly, overexpression of Hsf1 restores attenuated lipid accumulation caused by Usp39 deficiency. Taken together, our findings indicate that Usp39-mediated AS is crucial for sustaining lipophagy and lipid homeostasis in the liver. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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