CE12 - Génétique, génomique et ARN

RNA condensation and translation regulation upon physiological aging – POSTRAGING

Submission summary

Systems-wide analyses performed over the last 10 years have shown that a restricted number of genes undergo significant changes in expression upon aging. While recent comparative multi-omics studies have revealed that most of the age-dependent gene expression variations are explained by changes in translation regulation, how aging impacts specific sets of mRNAs is still unclear. This project aims at addressing the contribution of cytoplasmic ribonucleoprotein (RNP) condensates to age-dependent changes in translational repression. It is based on our recent discovery that hyper-condensation and decreased sorting selectivity are signatures of condensate aging.
Using two complementary model organisms, C. elegans and Drosophila, we propose to systematically characterize the landscape of transcripts undergoing age-dependent translation regulation in two types of long-lived cells: neurons and oocytes. Through integration of age-dependent changes in RNA condensation and translation profiles, and through combination of both transcriptomics and single molecule imaging, we will then molecularly and functionally dissect the connection between RNP condensate maturation and transcript-specific translation regulation.
With this multi-scale integrative study, we will thus provide the first comprehensive and mechanistic view on age-dependent, transcript-specific, translation regulation and its link to RNP condensate aging. Our work will also introduce major shifts in paradigm in the field of RNP condensates, as studies so far have focused on pathological rather than normal aging, and addressed the mechanisms promoting, rather than limiting, condensation.

Project coordinator

Madame Florence Besse (Centre national de la recherche scientifique)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

iBV Centre national de la recherche scientifique
iBV Centre national de la recherche scientifique

Help of the ANR 516,364 euros
Beginning and duration of the scientific project: March 2023 - 48 Months

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