LENG8 regulation of mRNA processing, is responsible for the control of mitochondrial activity
LENG8 regulation of mRNA processing, is responsible for the control of mitochondrial activity
ABSTRACT The processing of mRNA is essential for the maintenance of cellular and tissue homeostasis. However, the precise regulation of this process in mammalian cells, remains largely unknown. Here we have found that LENG8 represents the mammalian orthologue of the yeast mRNA processing factor Thp3 and Sac3. We go on to demonstrate that LENG8 binds to mRNAs, associates with components of mRNA processing machinery (the TREX complex) and contributes to mRNA nuclear export to the cytoplasm. Loss of LENG8, leads to aberrant accumulation of poly (A)+ RNA in the nucleus, in both Hela cells and murine fibroblasts. Furthermore, the precipitation of LENG8, is associated with an enrichment of both mRNAs and lncRNAs, and approximately half of these are also bound by the TREX component, THOC1. However, LENG8 preferentially binds mRNAs encoding for mitochondrial proteins and depletion of this processing factor, causes a dramatic breakdown in mitochondrial ultrastructure and a reduction in mitochondrial respiratory activity. Conditional deletion of Leng8 in mouse adipose tissues lead to a decreased body weight, and increased adipose thermogenesis. Our work has found an evolutionarily conserved mRNA processing factor that can control mitochondrial activity.
Mao Linfei、Xue Wenyue、Zhao Yongxu、Wang Xiaoting、Liu Yuenan、Guan Jian、Ding Qiurong、Wang Shengming、Gao Zhenfei、Zhang Xiaoxu、Sun Zhigang、Li Chunyan、Li Niannian、Yi Hongliang、Tang Ru、Liu Feng、Zhang Nan
Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of SciencesDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of SciencesDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Oncology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People?ˉs Hospital||Shanghai Key Laboratory of Sleep Disordered BreathingDepartment of Oncology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University
基础医学分子生物学生理学
mRNA processingLENG8TREXRNA-IPmitochondria
Mao Linfei,Xue Wenyue,Zhao Yongxu,Wang Xiaoting,Liu Yuenan,Guan Jian,Ding Qiurong,Wang Shengming,Gao Zhenfei,Zhang Xiaoxu,Sun Zhigang,Li Chunyan,Li Niannian,Yi Hongliang,Tang Ru,Liu Feng,Zhang Nan.LENG8 regulation of mRNA processing, is responsible for the control of mitochondrial activity[EB/OL].(2025-03-28)[2025-05-06].https://www.biorxiv.org/content/10.1101/2021.07.17.452750.点此复制
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