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

Summary
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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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101155345
Start date: 01-12-2024
End date: 30-11-2026
Total budget - Public funding: - 211 754,00 Euro
Cordis data

Original description

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.

Status

SIGNED

Call topic

HORIZON-MSCA-2023-PF-01-01

Update Date

25-11-2024
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.2 Marie Skłodowska-Curie Actions (MSCA)
HORIZON.1.2.0 Cross-cutting call topics
HORIZON-MSCA-2023-PF-01
HORIZON-MSCA-2023-PF-01-01 MSCA Postdoctoral Fellowships 2023