Active RNA interference in mitochondria.

TitleActive RNA interference in mitochondria.
Publication TypeJournal Article
Year of Publication2020
AuthorsGao, K, Cheng, M, Zuo, X, Lin, J, Hoogewijs, K, Murphy, MP, Fu, X-D, Zhang, X
JournalCell Res
Date Published2020 Aug 17
ISSN1748-7838
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.

DOI10.1038/s41422-020-00394-5
Alternate JournalCell Res.
Citation Key10.1038/s41422-020-00394-5
PubMed ID32807841
Grant List31670825 / / National Natural Science Foundation of China (National Science Foundation of China) /
2019YFA0508700 / / Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) /