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Active RNA interference in mitochondria.

Accepted version
Peer-reviewed

Type

Article

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Authors

Gao, Kuanxing 
Cheng, Man 
Zuo, Xinxin 
Hoogewijs, Kurt 

Abstract

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.

Description

Keywords

Animals, Argonaute Proteins, DNA, Mitochondrial, Fibroblasts, HEK293 Cells, HeLa Cells, Humans, Membrane Potential, Mitochondrial, Mice, Mitochondria, Myocytes, Cardiac, Oxygen, RNA Interference, RNA, Messenger, RNA, Small Interfering, Transfection

Journal Title

Cell Res

Conference Name

Journal ISSN

1001-0602
1748-7838

Volume Title

31

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_U105663142)
Wellcome Trust (110159/Z/15/Z)