mTOR-related linc-PMB promotes mitochondrial biogenesis via stabilizing SIRT1 mRNA through binding to the HuR protein

Mitochondrial dysfunction is implicated in numerous disorders, including type 2 diabetes, Alzheimer’s disease and cancer. Long non-coding RNAs (lncRNAs) are emerging as pivotal regulators of cellular energy metabolism, yet their roles remai...

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Main Authors: Chen Qian, Zhang Huaying, Wang Daokun, Liao Wenjing, Liu Yazhou, Cai Yurui, Wang Siyou, Yu Mengqian
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2025-01-01
Series:Acta Biochimica et Biophysica Sinica
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Online Access:https://www.sciengine.com/doi/10.3724/abbs.2024236
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Summary:Mitochondrial dysfunction is implicated in numerous disorders, including type 2 diabetes, Alzheimer’s disease and cancer. Long non-coding RNAs (lncRNAs) are emerging as pivotal regulators of cellular energy metabolism, yet their roles remain largely unclear. In this study, we identify an lncRNA named linc-PMB, which is associated with mTOR and promotes mitochondrial biogenesis, through microarray analysis. We demonstrate that the knockdown of linc-PMB results in significantly impaired mitochondrial respiration and biogenesis, along with altered expressions of related genes. Conversely, overexpression of linc-PMB markedly increases mitochondrial function. We further reveal that linc-PMB interacts with the RNA-binding protein HuR, promoting the stabilization of SIRT1 mRNA and a substantial increase in SIRT1 expression, which in turn activates the PGC-1α/mtTFA pathway and mitochondrial biogenesis. Collectively, our findings reveal a novel regulatory pathway in which linc-PMB, through its interaction with HuR, modulates the SIRT1/PGC-1α/mtTFA axis to maintain mitochondrial biogenesis and function.
ISSN:1672-9145