Translation Control in Development: when, where and how

ongoing

The translation of mRNAs by ribosomes is a key step in decoding the information stored in our genome. Animal development requires a strict regulation of translation, in particular when transcription is absent, as in most early embryos. A range of mechanisms ensure that mRNAs are translated with the right efficiency and location, in the right cell types and exactly when their protein products are needed. Disruption of this regulation can lead to developmental defects and embryonic lethality. Despite the recognized importance of translation regulation, the impact of translation regulation, and especially localized translation, on protein levels remains largely unknown for most genes. Furthermore, the mechanisms that drive localized and cell-type-specific translation are poorly understood, partly due to a lack of methods that enable the real-time visualization of translation in live embryos. The goal of this proposal is to discover translationally regulated mRNAs across the genome in early development, and reveal, with single-molecule precision, how spatiotemporal cues and cell type-specific mechanisms drive differential protein translation. Using ribosome profiling, we will create a genome-wide single-cell map of translation efficiencies during embryonic development of C. elegans, thus delineating the translation landscape that guides development. Using real-time single-molecule translation imaging, we will reveal how local translation patterns are formed and maintained between and within cells. Finally, we will explore how RNA-binding proteins modulate both translation efficiencies and spatial organization, to reveal the underlying mechanisms that drive translation during development. This combination of genome-wide and single-molecule studies will lay the groundwork for understanding how spatial cues and cell-type-specific mechanisms drive precise protein expression, which ultimately shapes cellular identity in early development.