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mRNA localization and spatial heterogeneity of translation: Deciphering the code within mRNP composition

Project description

Delineating the role of molecular complexes in development

RNA binding proteins (RBPs) assemble with messenger RNAs (mRNAs) to regulate their stability, localisation and translation within the cell. The generated messenger ribonucleoprotein (mRNP) particles play a central role in the post-transcriptional control of gene expression. Hundreds of RBPs have been identified, suggesting diverse mRNP assemblies for different mRNAs. Funded by the Marie Skłodowska-Curie Actions programme, the mRNPcode project aims to delineate how mRNP composition impacts mRNA fate. The work focuses on cell differentiation during development and will use Drosophila embryos to determine mRNP composition, localisation and translation heterogeneity. Results will provide a dynamic understanding of mRNA regulation.

Objective

mRNAs are packed with RNA binding proteins (RBPs) to assemble the messenger ribonucleoprotein particles (mRNPs). Proper mRNP biogenesis, export, localization, translation, and decay are central for gene expression regulation. Each step requires specific RBPs mediating transcript interactions with the cellular machinery. So far, hundreds of RBPs have been identified begging the question of mRNP assembly diversity. While canonical RBPs are associated with all transcripts, some may be accessory, concurrent, and specific for subclasses of mRNAs. What finetunes mRNP compositions is not clear and understanding how specific mRNP compositions control mRNA fate is a major challenge for RNA biology.
mRNA localization and regulated translation are believed to be mechanisms to delimit gene expression to cellular sub-compartments ensuring that proteins are synthesized where they complete their functions. Furthermore, some mRNAs display heterogeneous translation efficiencies depending on their localization in cells. mRNA localization and translation heterogeneity appear to be highly dynamic and can be fine-tuned upon cell differentiation, or during stress. These phenomena seem crucial during development, particularly for large syncytial cells such as Drosophila embryos but their prevalence and functions are not understood.
We hypothesize that mRNA localization and translation kinetics are encoded by the different combinations of RBPs assembling the mRNPs. We aim to decipher the link between mRNP composition, localization, and translation heterogeneity for key mRNAs controlling embryonic patterning in Drosophila embryos. The mRNPcode project will combine mRNP capture, proteomic, and cutting-edge microscopy for single particle tracking and translation imaging to build a dynamic picture of mRNP composition, localization, and translation. The project tackles long-lasting questions beyond the Drosophila developmental field by exploring mRNP assembly and its imprinting on mRNA fates.

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 211 754,88
Total cost

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