CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

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

doi:10.1016/j.jgg.2023.12.011

CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

J Genet Genomics. 2024 Jan 5:S1673-8527(24)00001-8. doi: 10.1016/j.jgg.2023.12.011. Online ahead of print.

Authors

Danhui Ruan¹, Jiancheng Xu¹, Yang Liu¹, Juan Luo², Xuyang Zhao¹, Yuhua Li¹, Guangxi Wang¹, Jiawen Feng¹, Hui Liang¹, Yue Yin³, Jianyuan Luo⁴, Yuxin Yin⁵

Affiliations

¹ 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.
² Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China.
³ Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
⁴ Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
⁵ 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; Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China. Electronic address: yinyuxin@hsc.pku.edu.cn.

PMID: 38184105
DOI: 10.1016/j.jgg.2023.12.011

Abstract

Phosphatase and tensin homolog (PTEN) is a multifunctional gene that is 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 posttranscriptional 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 Ι 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.

Keywords: Circular RNA; LRPPRC; Mitochondrial energy metabolism; mtDNA post-transcriptional regulation.