Epitranscriptome et plasticité cellulaire

Présentation

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.

Publications

• Marc Oudart, Katia Avila-Gutierrez, Clara Moch, Elena Dossi, Giampaolo Milior, Anne-Cécile Boulay, Mathis Gaudey, Julien Moulard, Bérangère Lombard, Damarys Loew, Alexis-Pierre Bemelmans, Nathalie Rouach, Clément Chapat, Martine Cohen-Salmon.
  The ribosome-associated protein RACK1 represses Kir4.1 translation in astrocytes and influences neuronal activity
  Cell Reports
  2023 May
• Limei Zou, Clara Moch, Marc Graille, Clément Chapat.
  The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex
  iScience
  2022 Jul
• Xu Zhang, Clément Chapat, Peng Wang, Jung-Hyun Choi, Qian Li, Jun Luo, Shane Wiebe, Sung-Hoon Kim, Nathaniel Robichaud, Isabela Fabri Karam, David Dai, Angela P Hackett, Rongtuan Lin, Tommy Alain, Long Yang, Seyed Mehdi Jafarnejad, Nahum Sonenberg.
  microRNA-induced translational control of antiviral immunity by the cap-binding protein 4EHP
  Molecular Cell
  2021 Mar
• Ditipriya Hazra, Clément Chapat, Marc Graille.
  m⁶A mRNA Destiny: Chained to the rhYTHm by the YTH-Containing Proteins
  Gene
  2019 Jan
• Seyed Mehdi Jafarnejad, Clément Chapat, Edna Matta-Camacho, Idit Anna Gelbart, Geoffrey G Hesketh, Meztli Arguello, Aitor Garzia, Sung-Hoon Kim, Jan Attig, Maayan Shapiro, Masahiro Morita, Arkady Khoutorsky, Tommy Alain, Christos G Gkogkas, Noam Stern-Ginossar, Thomas Tuschl, Anne-Claude Gingras, Thomas F Duchaine, Nahum Sonenberg.
  Translational control of ERK signaling through miRNA/4EHP-directed silencing
  eLife
  2018 Feb

Voir toutes les publications

Financements