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Doctoral thesis
English

Studying the Mitochondrial RNA granules: structure, compartmentalisation and regulation of their molecular content

Number of pages151
Imprimatur date2021-11-29
Defense date2021-11-24
Abstract

We decided to study the interactions between the Mitochondrial RNA granules (MRGs) and the mt-dsRNA foci using super-resolution STED microscopy. We found that dsRNA foci are part of the MRGs, where they form a distinct, but overlapping nanodomain with the ss-RNA core of MRGs. Furthermore, dsRNA foci colocalize with GRSF1 and to a lesser extent with FASTKD2, two protein components of MRGs. In addition, we show that the degradosome component SUV3 has a dual localization, within and outside MRGs.It had also been reported that mt-dsRNA is undetectable in primary cells unlike in cancer cells. To investigate this observation further, we generated an in vitro model of cancer where human primary dermal fibroblasts have been transformed into malignant cells. We determined that dsRNA foci were observed after the induction of oncogenes. The process of tumourigenesis increased the total amount of MRGs, mtDNA and mitochondrial mass and mt-transcription. We posited that the total cellular proliferation of carcinogenic cells was linked to the increase in transcription and regulation of the mitochondrial genome.

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Citation (ISO format)
XAVIER, Vanessa Joanne. Studying the Mitochondrial RNA granules: structure, compartmentalisation and regulation of their molecular content. 2021. doi: 10.13097/archive-ouverte/unige:158187
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