Spatio-temporal coupling between transcription and translation dynamics during development

Introduction

During development, precise control of gene expression allows the reproducible establishment of patterns, leading to the adoption of cellular identities at the right time and place. What are the mechanisms behind such precision?

Background

To date, this question has been primarily examined from the focal point of transcription. However, precision in mRNA production is functionally relevant only if it leads to precision in protein expression. While the linear correlation between the levels of a given mRNA and the amount of protein it encodes has been assumed for the last six decades within the central dogma of molecular biology, many examples challenge this view.

Mechanisms of Translation Control

The control of translation, particularly in distinct subcellular compartments where mRNAs are targeted, may lie at the heart of this mRNA to protein disconnect. LightRNA2Prot aims to unravel the mechanisms underlying the lack of correlation between mRNA and protein levels to elucidate the sources of reproducible cell fate decisions during development.

Regulatory Layers

Importantly, it considers both the layers of regulation constituted by transcription and translation respectively, as well as their potential coupling.

Methodology

We will use quantitative imaging methods that simultaneously monitor mRNA, nascent peptides, and protein in Drosophila living embryos, combined with genetic/optogenetic manipulations to dissect the mechanisms at play.

Key Questions

LightRNA2Prot focuses on two key questions:

1. How do the translation dynamics of key localized developmental transcripts modulate precise patterning?
2. How are (co)-transcriptional nuclear events coordinated with translational control in space and time?

Expected Outcomes

Combined with mathematical modeling and phenotypic characterization, our quantitative approaches will provide a dynamic multiscale view of gene expression control in vivo. The novel integration of translational control has the potential to dramatically change our view of stereotypic pattern formation and reproducible cell fate decisions during development.