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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author Chen Qian
Zhang Huaying
Wang Daokun
Liao Wenjing
Liu Yazhou
Cai Yurui
Wang Siyou
Yu Mengqian
author_facet Chen Qian
Zhang Huaying
Wang Daokun
Liao Wenjing
Liu Yazhou
Cai Yurui
Wang Siyou
Yu Mengqian
author_sort Chen Qian
collection DOAJ
description 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.
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institution Kabale University
issn 1672-9145
language English
publishDate 2025-01-01
publisher China Science Publishing & Media Ltd.
record_format Article
series Acta Biochimica et Biophysica Sinica
spelling doaj-art-cd0ecb78e10a42f4b691d4bbde9734eb2025-08-20T03:59:35ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452025-01-01571057106710.3724/abbs.202423620d259ccmTOR-related linc-PMB promotes mitochondrial biogenesis via stabilizing SIRT1 mRNA through binding to the HuR proteinChen Qian0Zhang Huaying1Wang Daokun2Liao Wenjing3Liu Yazhou4Cai Yurui5Wang Siyou6Yu Mengqian7["Department of Laboratory Medicine, Chengdu Second People’s Hospital, Chengdu 610017, China"]["Department of Clinical Laboratory, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310000, China"]["Department of Laboratory Medicine, Chengdu Second People’s Hospital, Chengdu 610017, China"]["Department of Laboratory Medicine, Chengdu Second People’s Hospital, Chengdu 610017, China"]["Department of Laboratory Medicine, Chengdu Second People’s Hospital, Chengdu 610017, China"]["Department of Laboratory Medicine, Chengdu Second People’s Hospital, Chengdu 610017, China"]["Department of Laboratory Medicine, Chengdu Second People’s Hospital, Chengdu 610017, China"]["Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310000, China"]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.https://www.sciengine.com/doi/10.3724/abbs.2024236HuRlong non-coding RNAmitochondrial biogenesismTORSIRT1
spellingShingle Chen Qian
Zhang Huaying
Wang Daokun
Liao Wenjing
Liu Yazhou
Cai Yurui
Wang Siyou
Yu Mengqian
mTOR-related linc-PMB promotes mitochondrial biogenesis via stabilizing SIRT1 mRNA through binding to the HuR protein
Acta Biochimica et Biophysica Sinica
HuR
long non-coding RNA
mitochondrial biogenesis
mTOR
SIRT1
title mTOR-related linc-PMB promotes mitochondrial biogenesis via stabilizing SIRT1 mRNA through binding to the HuR protein
title_full mTOR-related linc-PMB promotes mitochondrial biogenesis via stabilizing SIRT1 mRNA through binding to the HuR protein
title_fullStr mTOR-related linc-PMB promotes mitochondrial biogenesis via stabilizing SIRT1 mRNA through binding to the HuR protein
title_full_unstemmed mTOR-related linc-PMB promotes mitochondrial biogenesis via stabilizing SIRT1 mRNA through binding to the HuR protein
title_short mTOR-related linc-PMB promotes mitochondrial biogenesis via stabilizing SIRT1 mRNA through binding to the HuR protein
title_sort mtor related linc pmb promotes mitochondrial biogenesis via stabilizing sirt1 mrna through binding to the hur protein
topic HuR
long non-coding RNA
mitochondrial biogenesis
mTOR
SIRT1
url https://www.sciengine.com/doi/10.3724/abbs.2024236
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