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Identification of mecciRNAs and their roles in the mitochondrial entry of proteins

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Abstract

Mammalian mitochondria have small genomes encoding very limited numbers of proteins. Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria. Here, we report the identification of hundreds of circular RNAs (mecciRNAs) encoded by the mitochondrial genome. We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins. Known components involved in mitochondrial protein and RNA importation, such as TOM40 and PNPASE, interact with mecciRNAs and regulate protein entry. The expression of mecciRNAs is regulated, and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation. mecciRNAs and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.

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Data availability

All RNA-seq and DNA resequencing data are deposited in the NCBI with the accession number.

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Acknowledgements

We thank Lei Liu for technical support of C. elegans experiments. This work was supported by grants to G. S.: the National Key R&D Program of China (2019YFA0802600 and 2018YFC1004500), the National Natural Science Foundation of China (31725016, 31930019, and 91940303), and the Strategic Priority Research Program (Pilot Study) “Biological basis of aging and therapeutic strategies” of the Chinese Academy of Sciences (XDPB10).

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  1. Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, 230027, China

    Xu Liu, Xiaolin Wang, Jingxin Li, Yuqi Deng, Hao Yin, Baolong Wang, Qinghua Shi & Ge Shan

  2. Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, 230001, China

    Shanshan Hu

  3. Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Medical University and Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China

    Xichen Bao

  4. MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, 100084, China

    Qiangfeng Cliff Zhang & Geng Wang

  5. CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China

    Qinghua Shi & Ge Shan

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  1. Xu Liu
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  2. Xiaolin Wang
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Correspondence to Ge Shan.

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Liu, X., Wang, X., Li, J. et al. Identification of mecciRNAs and their roles in the mitochondrial entry of proteins. Sci. China Life Sci. 63, 1429–1449 (2020). https://doi.org/10.1007/s11427-020-1631-9

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