The "Epitranscriptome and Cell Plasticity" Lab: Exploring how physical intimacy between translation apparatus and mRNA silencing machineries shapes the proteome
The proteome is defined as the set of proteins produced by a cell, and varies considerably from one cell to another depending on its type, function, the tissue in which it resides and the signals it receives from its environment. A cell’s homeostasis is therefore intimately orchestrated by the composition and quality of its proteome, and depends on how its transcriptome is handled by the translation apparatus. During translation, the ribosome, assisted by transfer RNAs (tRNAs), decodes messenger RNAs (mRNAs) to produce the corresponding proteins. The term “translatome” has been proposed to define the population of mRNAs directly involved in translation at any given time.
The post-transcriptional regulations of the human translatome represent a new terra incognita to be explored in biology. Post-transcriptional silencing mechanisms modulate mRNA stability and translation, contributing to the rapid and flexible control of protein synthesis. This phenomenon mainly relies on the repressive activity of various mRNA-driven machineries which can be mobilized by microRNAs, RNA-binding proteins and mRNA modifications. Recent data showed that silencing machineries have a selective activity based on the codon composition of the targeted mRNA. Why and how these machineries promote a bidirectional modulation of mRNA translation and decay based on codon usage remains an outstanding question. With this in mind, our research at the Centre for Integrative Biology of Toulouse aims to investigate the mechanisms that link the translation apparatus with mRNA silencing machineries, and how this interaction drives cell-fate decisions. In particular, we seek to set up an integrated experimental framework to measure the impact of ribosome-targeting by mRNA decay factors on translational landscapes. Altogether, our results open a fascinating window into our understanding of how a physical intimacy between mRNA silencing machineries and translation apparatus shapes the ever-changing swarm of proteins that differs from cell to cell.