Mitochondrial targeting of RNA : mechanisms, functions and tool for therapy

Abstract

Mitochondria import from the cytosol several types of small nuclear DNA encoded RNAs, which participate in mtDNA replication, RNA processing or translation. We studied mechanistic and functional implications of tRNA mitochondrial import in yeast and of 5S rRNA in mammalian cells and attempted to exploit it as a therapeutic tool to address mitochondrial diseases, a large group of incurable pathologies caused by mutations in either nuclear or mitochondrial DNA. We found that altered mitochondrial RNA import pathway may have important pathological consequences. We also demonstrated that RNA import can be exploited to target into mitochondria oligoribonucleotides capable to specifically inhibit replication or affect copy number of mtDNA molecules. This study was supported by the LabEx MitoCross, ANR, FRM, the CNRS and the University of Strasbourg.