Volume 31, No 2, Feb 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 2, February 2021: 219-228

ORIGINAL ARTICLES

Active RNA interference in mitochondria

Kuanxing Gao^1,2 , Man Cheng² , Xinxin Zuo¹ , Jinzhong Lin³ , Kurt Hoogewijs⁴ , Michael P. Murphy^5,6 , Xiang-Dong Fu^7,* , Xiaorong Zhang^2,*

¹State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China
²Key Laboratory for RNA Biology, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China
³State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China
⁴Department of Organic and Macromolecular Chemistry, University of Ghent, Ghent 9000, Belgium
⁵Medical Research Council-Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 1TN, UK
⁶Department of Medicine, University of Cambridge, Cambridge CB2 1TN, UK a
⁷Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA
These authors contributed equally: Kuanxing Gao, Man Cheng Correspondence: Xiang-Dong Fu(xdfu@ucsd.edu)Xiaorong Zhang(xrzhang@ibp.ac.cn)

RNA interference (RNAi) has been thought to be a gene-silencing pathway present in most eukaryotic cells to safeguard the genome against retrotransposition. Small interfering RNAs (siRNAs) have also become a powerful tool for studying gene functions. Given the endosymbiotic hypothesis that mitochondria originated from prokaryotes, mitochondria have been generally assumed to lack active RNAi; however, certain bacteria have Argonaute homologs and various reports suggest the presence of specific microRNAs and nuclear genome (nDNA)-encoded Ago2 in the mitochondria. Here we report that transfected siRNAs are not only able to enter the matrix of mitochondria, but also function there to specifically silence targeted mitochondrial transcripts. The mitoRNAi effect is readily detectable at the mRNA level, but only recordable on relatively unstable proteins, such as the mtDNA-encoded complex IV subunits. We also apply mitoRNAi to directly determine the postulated crosstalk between individual respiratory chain complexes, and our result suggests that the controversial observations previously made in patient-derived cells might result from differential adaptation in different cell lines. Our findings bring a new tool to study mitochondrial biology.

https://doi.org/10.1038/s41422-020-00394-5

FULL TEXT | PDF

Browse 1165