CE12 - Génétique, génomique et ARN

Elucidating the translation switch regulating cell division – OffOnCYTE

Submission summary

Cell division is a crucial aspect of cellular physiology and plays a pivotal role in biological processes, such as reproduction, development, tissue repair and growth. The cellular choice to commit to division is a complex decision that is driven by various molecular signaling pathways. One of the emerging layers involved in this decision making is de novo protein translation, which provides new proteins required for cell division.
Despite its importance, the regulation of de novo protein translation during cell division remains poorly understood. The study of this process has been limited by the intricate interplay between transcription and translation regulations, making it challenging to isolate the effects of specific changes in the translation program on cell division. To overcome this drawback, the OffOnCYTE project aims to use meiotic division as a cell division paradigm and Xenopus laevis oocytes as an experimental system.
In response to an external physiological stimulus, vertebrate oocytes undergo a translation reprogramming that triggers entry into M-phase, the phase of cell division. This translation reprogramming occurs in the absence of transcription, making it an ideal system for studying the regulation of de novo protein translation during cell division. Xenopus laevis oocytes are giant cells, containing high amounts of proteins and RNAs and easy to be microinjected, therefore highly suitable for studying protein translation. Thanks to these features, this model system provides the unique opportunity to combine single-cell approaches with large-scale biochemical and genomic techniques.
By coupling unbiased genome-wide approaches and functional studies, the OffOnCYTE project aims to unravel how the cell decision to enter M-phase is coded into a translation switch. Specifically, the project will identify novel mRNAs whose translation controls the entry into cell division and will highlight new molecular mechanisms regulating mRNA translation.
To achieve these goals, the OffOnCYTE project will employ a range of cutting-edge techniques, including ribosome profiling, mass spectrometry and RNA sequencing. Coupled with well-established functional approaches in the Xenopus oocyte, these techniques will allow to comprehensively analyze changes in the translation program during cell division and to identify the key molecular players that regulate this process.
Overall, the OffOnCYTE project will provide important insights into the regulation of de novo protein translation that triggers cell division. The understanding of the molecular mechanisms that control this process will pave the way for the development of new strategies for controlling cell division in various biological contexts, such as oncology and biology of reproduction.

Project coordination

Enrico Maria Daldello (LBD - Laboratoire de Biologie du développement)

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

LBD LBD - Laboratoire de Biologie du développement

Help of the ANR 324,500 euros
Beginning and duration of the scientific project: February 2024 - 36 Months

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