首页|CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

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Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins.However,PTEN-related circRNAs are largely unknown.Here,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism.CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates post-transcriptional gene expression in mitochondria.Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex Ⅰ subunit and reduces mitochondrial membrane potential and adenosine triphosphate production.Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism.This study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.

Circular RNALRPPRCMitochondrial energy metabolismmtDNA post-transcriptional regulation

Danhui Ruan、Jiancheng Xu、Yang Liu、Juan Luo、Xuyang Zhao、Yuhua Li、Guangxi Wang、Jiawen Feng、Hui Liang、Yue Yin、Jianyuan Luo、Yuxin Yin

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Institute of Systems Biomedicine,Department of Pathology,School of Basic Medical Sciences,Beijing Key Laboratory of Tumor Systems Biology,Peking University International Cancer Institute,Peking-Tsinghua Center of Life Sciences,Peking University Health Science Center,Beijing 100191,China

Soochow University Cancer Institute,Suzhou,Jiangsu 215127,China

Institute of Precision Medicine,Peking University Shenzhen Hospital,Shenzhen,Guangdong 518036,China

Department of Pharmacology,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China

Department of Medical Genetics,Center for Medical Genetics,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China

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国家自然科学基金国家自然科学基金国家重点研发计划Shenzhen High-level Hospital Construction Fund and Shenzhen Basic Research Key ProjectScholar of the Lam Chung Nin Foundation for Systems BiomedicinePostdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences

82030081818742352021YFA1300601JCYJ20220818102811024

2024

10.1016/j.jgg.2023.12.011

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(5)
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