Identification of mecciRNAs and their roles in the mitochondrial entry of proteins
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entification of mecciRNAs and their roles in the mitochondrial entry of proteins 1
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Xu Liu , Xiaolin Wang , Jingxin Li , Shanshan Hu , Yuqi Deng , Hao Yin , Xichen Bao , 4 4 1 1,5 1,5* Qiangfeng Cliff Zhang , Geng Wang , Baolong Wang , Qinghua Shi & Ge Shan 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; Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, China; 3 Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Medical University 2
and Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; 4 MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China; 5 CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China Received January 13, 2020; accepted January 14, 2020; published online January 21, 2020
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. mitochondria, circRNA, mecciRNA, mitochondrial protein import Citation:
Liu, X., Wang, X., Li, J., Hu, S., Deng, Y., Yin, H., Bao, X., Zhang, Q.C., Wang, G., Wang, B., et al. (2020). Identification of mecciRNAs and their roles in the mitochondrial entry of proteins. Sci China Life Sci 63, https://doi.org/10.1007/s11427-020-1631-9
INTRODUCTION Mammalian mitochondria harbor their own genome encoding 13 mitochondrial-specific proteins and multiple noncoding RNAs, such as 16S rRNA and some tRNAs (Anderson et al., 1981; Gustafsson et al., 2016). These proteins and RNAs represent a very small fraction o
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