Biology subjects

Benassy, M.-N.

Publications and source records attributed to Benassy, M.-N..

3 recordsLinked to original sources

bioRxiv2026

Loss of MTPAP disrupts mitochondrial RNA processing causing upregulation of type I interferon signalling

Mitochondrial poly-A polymerase (MTPAP) is essential for mitochondrial mRNA (mt-mRNA) polyadenylation, a critical step in mt-mRNA maturation. Mutations in MTPAP have been reported to cause a mitochondrial cytopathy. Here, we provide evidence of enhanced type I interferon (IFN) signalling in the blood of patients carrying mutations in MTPAP. Further, deletion of MTPAP in a fibroblast cell model led to abnormalities in mitochondrial respiration and mtRNA processing, and an upregulation of type I IFN signalling. Notably, both in patients fibroblast and in MTPAP-deleted cells, we observed the accumulation of non-coding mtRNA and mitochondrial double-stranded RNA (mt-dsRNA) within enlarged mitochondrial RNA granules. Cytosolic release of mt-dsRNA led to type I IFN induction mediated primarily by the RNA sensor MDA5 and its adaptor MAVS. Our findings reveal a novel consequence of MTPAP dysfunction, highlighting how impaired mtRNA maturation can drive innate immune system activation.

cell biology↗

bioRxiv2024

Cell cycle-dependent mRNA localization in P-bodies

Understanding the dynamics of RNA targeting to membraneless organelles is essential to disentangle their functions. Here, we investigate how P-bodies (PBs) evolve during cell cycle progression. PB purification across the cell cycle uncovers widespread changes in their RNA content, which are partly uncoupled from cell cycle-dependent changes in RNA expression. Single molecule FISH shows various mRNA localization patterns in PBs peaking in G1, S, or G2, with examples illustrating the timely capture of mRNAs in PBs when their encoded protein becomes dispensable. Yet, rather than directly reflecting absence of translation, cyclic mRNA localization in PBs can be controlled by RBPs, such as HuR in G2, and by RNA features. Indeed, while PB mRNAs are AU-rich at all cell cycle phases, they are specifically longer in G1, possibly related to post-mitotic PB reassembly. Altogether, our study supports a model where PBs are more than a default location for excess untranslated mRNAs.

cell biology↗

bioRxiv2022

Condensate functionalization with motors directs their nucleation in space and allows manipulating RNA localization

The localization of RNAs in cells is critical for many cellular processes. Whereas motor-driven transport of RNP condensates plays a prominent role in RNA localization in cells, their studies remain limited by the scarcity of available tools allowing to manipulate condensates in a spatial manner. To fill this gap, we reconstitute in cellula a minimal RNP transport system based on bioengineered condensates which were functionalized with kinesins and dynein-like motors, allowing for their positioning at either the cell periphery or centrosomes. This targeting mostly occurs through the active transport of the condensate scaffolds, which leads to localized nucleation of phase-separated condensates. Then, programming the condensates to recruit specific mRNAs is able to shift the localization of these mRNAs towards the cell periphery or the centrosomes. Our method opens novel perspectives to examine the role of RNA localization as a driver of cellular functions.

cell biology↗