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Team 1 : Intracellular traffic of RNA and mitochondrial pathologies

Team leaders: Ivan TARASSOV & Nina ENTELIS

Research topics

The team is a part of the GMGM (partner 1). The team tends to decrypt molecular mechanisms of nucleo-mitochondrial traffic of RNA and to exploit this pathway as a therapeutic tool. Two main objectives of this team will be (i) to understand detailed molecular mechanisms of mitochondrial import of nuclear DNA encoded RNAs and (ii) to exploit this RNA import pathway to develop new tools of gene therapy of mtDNA - associated mitochondrial pathologies.


Role in MitoCross

The first task will be the understanding of the fine molecular mechanisms of RNA mitochondrial import pathway. Within this main objective the team will study the mechanism of RNA translocation across mitochondrial membranes, the functions of nuclear-encoded RNAs in mitochondria and RNA import regulation as a part of nuclear-mitochondrial crosstalk.

The second task will be to exploit RNA mitochondrial import as a therapeutic tool. We lastly were able to demonstrate that pathogenic mutations in mitochondrial tRNA genes can be addressed by targeting specifically designed tRNAs into human mitochondria. So far, this approach (called "allotopic", for expressing mitochondrial macromolecules in the nuclear environment) can be exploited only to a portion of pathogenic mutations in mtDNA. A more generalized approach would be to exploit the fact that the vast majority of these mutations are "heteroplasmic", meaning the simultaneous presence of mutant and wild type genomes, the pathology manifesting only above a high threshold of >70% of mutant ones. We therefore are currently developing such an "antigenomic" strategy, by use of mitochondrially targeted RNAs as vectors for oligoribonucleotides specifically affecting the replication of mutant mtDNA without affecting that of  wild type genomes.

The third task will be to addressthe mechanisms of pathogenesis affecting mitochondrial translation. The team expect to continue the fruitful collaboration with clinical and periclinical laboratories working in the domain of mitochondrial pathologies. Our expertise in RNA biology and mitochondrial function analysis will permit understanding of molecular mechanisms of human diseases causing defects in mitochondrial translation.


Current members

Former members

  • Damien Jeandard, Thèse de Doctorat soutenue le 1er Février 2019
  • Romuald Loutre, Thèse de Doctorat soutenue le 11 Décembre 2017
  • Maria Baleva, Thèse de Doctorat soutenue le 16 Décembre 2016 (Co-supervised by P. Kamenski, Moscow State University)
  • Ivan Chicherin, Thèse de Doctorat soutenue le 6 Octobre 2016 (Co-supervised by P. Kamenski, Moscow State University)
  • Ilya Dovydenko, Thèse de Doctorat soutenue le 23 Septembre 2015

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Dec 7 2023

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